Clinical trial NCT04034251
Conditions: Gastric Adenocarcinoma Gastric Cancer Esophagogastric Junction Peritoneal Carcinomatosis
Keywords: Gastroesophageal Junction (Siewert III) Adenocarcinoma Intravenous Chemotherapy Progression Free Survival Peritoneal Metastasis Intraperitoneal Chemotherapy
Sponsor: National Cancer Institute (NCI)
Start date: 2020-06-09; Completion date: 2024-09-05
Enrollment: 12 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Background:

Three-fourths of people diagnosed with gastric cancer will die from it. Researchers want to see if giving cancer drugs in a new way can help people live longer and delay the time it takes for the cancer to grow.

Objective:

To find a better way to treat advanced stomach cancer.

Eligibility:

People ages 18 and older with stomach cancer that has spread throughout their belly.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood, urine, and heart tests

Scans

Cancer sample: If they do not have one, they will have a biopsy.

Tests of performance of normal activities

Dietary assessment

Participants will have a laparoscopy. Small cuts are made into their abdomen. A thin camera with a light is inserted. Small instruments are used to take biopsies. This will be repeated during the study to monitor the cancer. During the first laparoscopy, a port with a catheter attached will be put into the abdomen.

Participants may also have an endoscopy: A thin tube with a camera is inserted through the mouth and into the stomach. The tube collects samples to monitor the cancer.

Participants will get paclitaxel every 3 weeks through the abdominal port and through a small plastic tube in an arm vein. They will also take capecitabine by mouth twice daily for the first 15 days of a 21-day cycle.

After participants finish 3 cycles, they will have scans to see how they are doing. They may get another course of therapy.

Participants will have visits every 3 weeks during treatment. Then they will have follow-up visits for 5 years. Then they will keep in touch with researchers for the rest of their life.

Detailed description:
Background:

* An estimated 28,000 cases of gastric adenocarcinoma are diagnosed annually in the United States (U.S.)
* Peritoneal metastasis is a common finding at diagnosis, making curative surgical resection possible in an estimated 25% of patients.
* Systemic chemotherapy is the recommended treatment for patients with metastatic gastric cancer to the peritoneal cavity, however selective use of cytoreductive surgery and intraperitoneal chemotherapy has been associated with improved overall survival.
* Multiple chemotherapeutic agents and delivery systems have been described for intraperitoneal therapy, but no standard regimen exists.

Objective:

-Determine the intraperitoneal progression free survival (iPFS) in patients with peritoneal metastases from gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) and systemic paclitaxel administration with concomitant capecitabine therapy.

Eligibility:

* Histologically confirmed adenocarcinoma of the stomach.
* Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence of peritoneal carcinomatosis found at staging laparoscopy.
* Medically fit for systemic chemotherapy and intraperitoneal chemotherapy.
* Men and women age greater than or equal to 18 years.

Design:

* Phase II, nonrandomized, open label study.
* Patients will enroll in two cohorts: those with prior systemic chemotherapy and those who are treatment naive.
* Patients undergo staging laparoscopy and placement of peritoneal access port.
* Intraperitoneal paclitaxel (60 mg/m\^2 weekly), intravenous paclitaxel (80 mg/m\^2 weekly), and capecitabine (825 mg/m\^2 twice daily for 14 days of each cycle) for 12 weeks.
* Treatment response will be assessed with imaging and laparoscopy.
* It is expected that 16-20 patients per year for total 4 years will be enrolled. The accrual ceiling is set at 74 patients.

Arms: arm 1: Intraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine arm 2: Intraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine arm 3: Intraperitoneal (IP) and intravenous (IV) paclitaxel administration with concomitant oral capecitabine
Interventions: intervention 1: Paclitaxel intervention 2: Capecitabine intervention 3: BardPort Titanium Implanted Port with Peritoneal Catheter
Intervention descriptions: intervention 1: Paclitaxel (intraperitoneal (IP) and intravenous (IV), Day 1 of each 3-week cycle: Paclitaxel IP - Intraperitoneal paclitaxel (60 mg/m\^2) will be diluted in 500 mL of 0.9% normal saline (NS), to be infused as rapidly as tolerated once per 3-week cycle on Day 1. Paclitaxel IV - Intravenous paclitaxel (80 mg/m\^2) will be administered concomitantly over 3 hours, diluted in 100 to 250 ml of 0.9% NS once per 3-week cycle on Day 1. intervention 2: Day 1-15 of each 3-week cycle: oral capecitabine (825 mg/m\^2) to be taken twice a day starting the evening of Day 1 of each cycle until the morning of Day 15, followed by a 7-day rest period during each 3-week cycle. intervention 3: After peritoneal chemo infusion port is placed (Days 1-3, as dictated by clinical status), patients will begin intraperitoneal paclitaxel and intravenous paclitaxel (Day 1) followed by oral capecitabine on the evening of Day 1 to the morning of Day 15.

Protocol documents:
ICF_001.pdf: 
PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 06/01/2022
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:
Jeremy L. Davis, MD 
STUDY TITLE: 
A Phase II Study of Intraperitoneal and Intravenous 
Paclitaxel Chemotherapy with Oral Capecitabine for Gastric 
Adenocarcinoma with Peritoneal Carcinomatosis
STUDY SITE: 
NIH Clinical Center
Cohort:                                         
Affected Patients 
Consent Version:       
06/01/2022
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Principal Investigator:
Jeremy L. Davis, MD 
Phone: 240-858-3731 
Email: jeremy.davis@nih.gov   
KEY INFORMATION ABOUT THIS RESEARCH 
This consent form describes a research study and is designed to help you decide if you would 
like to be a part of the research study.  
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
This section provides the information we believe is most helpful and important to you to in 
making your decision about participating in this study. Additional information that may help 
you make a decision can be found in other sections of the document. Taking part in research at 
the NIH is your choice.
You are being asked to join this study because you have stomach cancer that has spread 
throughout your abdomen. Your study doctor thinks this study may be an option for you.
The purpose of this study is to find a better way to treat stomach cancer.  We want to see if 
standard chemotherapy drugs given in a new way can help you live longer and delay the time 
that it takes for the cancer to get worse (progress).  
Paclitaxel and capecitabine are used to treat several cancers including stomach cancer. Paclitaxel 
is usually given into the vein and capecitabine is given by mouth. In this study, you will receive 
paclitaxel through a vein and directly into your abdomen. 
Paclitaxel, but not capecitabine, is approved by U.S. Food and Drug Administration (FDA) for 
treatment of stomach cancer. However, capecitabine is often used to treat stomach cancer 
because there is strong evidence that it is effective. 
There are other drugs that could be used to treat your disease, and these can be given by your 
regular cancer doctor if you do not take part in this study. For example: cisplatin, abraxane and 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


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docetaxel are some possible treatments that you could receive. These options are similar to the 
drugs being used in this study.  
If you decide to join this study, here are some of the most important things you should know 
that will happen: 
•We will perform tests (screening) to find out if you are able to take part in this study such as:  
complete physical examination, blood and urine tests, and imaging (such as CT, MRI, and PET 
scans). 
•We will ask you to complete questionnaires and will collect samples (such as blood and tumor 
tissue) from you for research purposes, including genetic testing.  
•We will review a sample of your cancer from a previous surgery to confirm your diagnosis of 
stomach cancer. If a sample of your cancer is not available, we will need to do a new biopsy.
•If you are a woman who can have children, you will not be able to participate in this study if 
you are pregnant. You will need to avoid becoming pregnant during your participation in this 
study. 
•If you are a sexually active person with a partner capable of becoming pregnant, you and your 
partner will need to agree to use birth control if you want to take part in this study. It is important 
that your partner not become pregnant during your participation in this study.
If you are eligible to take part and decide to join this study:
•You will have an exploratory surgery procedure, called a laparoscopy. This is a surgical 
procedure that allows us to examine the inside of the abdomen, so we can see how much your 
cancer has spread. In this procedure, small cuts will be made into your abdomen and a thin tube 
with a light and a camera will be inserted. You will be given a medication so that you sleep 
through the procedure.  You’ll be admitted to the hospital to have this procedure and you will 
be discharged a day later.
You will also have a laparoscopy procedure done at the end of the first and second cycles of 
treatment, to find out whether or not the treatment has worked on the cancer in your abdomen.
•During the first laparoscopy, you will have an Intraperitoneal (IP) port inserted which involves 
placing a port under the skin on your abdomen, attaching a catheter to it and putting the catheter 
into your abdomen. This is what we will use to deliver the paclitaxel into your abdomen. 
•You will begin treatment with paclitaxel which is given as an intravenous (IV) infusion. A 
small plastic tube is put into a vein in your arm and the medication is given once every three 
weeks. Paclitaxel will also be given through a tube directly into your abdomen, so the drug can 
reach your tumors directly. You will receive paclitaxel in the Oncology Outpatient Center every 
three weeks during the treatment portion of the study. These visits will take 4-6 hours. 
•Giving paclitaxel directly into your abdomen is not an FDA approved procedure, which means 
the way we are giving you this medication is considered investigational. 
•Capecitabine is taken by mouth. You will take capecitabine twice a day starting the evening of 
Day 1 and continue through the morning of Day 15 in a 21-day cycle. After 14 days you will 
enter a 7-day rest period. 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
•After you finish the first three cycles of treatment (one course), you will receive tests to see 
how you are doing and to see how your disease is responding. You may be able to receive up to 
two courses of therapy if your cancer has not worsened. 
•You will be seen in the NIH Clinical Center by your study team every three weeks (Weeks 1, 
4, and 7) while you are receiving treatment. After treatment, you will be seen on a less frequent 
basis and we would like to keep in touch with you for the rest of your life. This is described later 
in this consent. 
As described later in more detail in this consent form, you may have side effects if you take part 
in this study. Some can be mild or very serious, temporary, long-lasting, or permanent, and may 
include death.  
The most frequent side effects of paclitaxel are nausea, vomiting, diarrhea, low blood counts 
and difficulty swallowing. The most frequent side effects of capecitabine are swelling, blisters, 
redness, pain, diarrhea, sores, fever and anemia. Risks are explained in detail later in consent. 
Please talk to your study doctor or other members of the study team if have any questions 
regarding risks or alternative treatments. 
Just as we do not know what side effects you might have, we cannot know if you may benefit 
from taking part in this study. If you do not receive any benefit, this study and the results from 
our research will help others in the future.
If you would rather just get standard chemotherapy for your disease, or if you do not want to 
undergo any laparoscopies, or to get chemotherapy in your abdomen, you should not join this 
trial.
You are free to stop participating in the trial at any time.  If you decide to stop, the study doctor 
may ask you to agree to certain tests to make sure it is safe for you to stop.
The remaining document will now describe more about the research study.  This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information described in this document. Some people have personal, religious, or ethical 
beliefs that may limit the kinds of medical or research treatments they would want to receive (such 
as blood transfusions). Take the time needed to ask any questions and discuss this study with NIH 
staff, and with your family, friends, and personal health care providers.
The individual being asked to participate in this research study is not able to give consent to be in 
this study. Therefore, you are being asked to give permission for this person as their decision-
maker. The term “you” refers to you as the decision-maker and/or the individual being asked to 
participate in this research, throughout the remainder of this document. 
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
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PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
WHY IS THIS STUDY BEING DONE?
This is a research study. The main purpose of this study is to see if standard chemotherapy drugs 
given directly into your abdomen as well as by vein can help you live longer and delay the time 
that it takes for the cancer to get worse (progress).
WHAT WILL HAPPEN DURING THE STUDY?
Before You Begin the Study
You will have several tests performed to be certain it is safe for you to start this treatment, 
including:

Medical history and physical exam 

You will provide a sample of your cancer from a previous surgery so we can confirm 
your diagnosis. If a sample is not available, we will need to do a new biopsy.
You may receive conscious sedation before undergoing a biopsy, if needed, and you will 
be informed of the additional risks prior to undergoing the procedure. Conscious sedation 
is usually given to help someone relax and minimize discomfort. It can be given as a pill, 
a shot, an IV or even inhaled. You may have to wait up to an hour to start feel the effects 
depending on how it is given. Once it takes effect, you will be mostly awake, though 
relaxed or drowsy. You will be monitored throughout the procedure. If your biopsy will 
be done during laparoscopy (a minor surgery) you will be given general anesthesia 
instead, as indicated below in the section During the Study. The study doctor will let you 
know if this is the case. 

Vital signs 

Assess your ECOG performance status (ECOG measures your ability to perform your 
normal activities)

EKG to check your heart

Dietary assessment

Routine blood (~7 tablespoons) and urine tests

Pregnancy test (~1 teaspoon blood sample) if you are a woman who can have children.

CT scan with or without PET scans

Tests for Hepatitis B and C (~2 teaspoons)

HIV testing (~1 teaspoon)
As part of this study, we will test you for infection with the human immunodeficiency 
virus (HIV), the virus that causes AIDS.  If you are infected with HIV an infectious 
disease specialist will decide if you can still participate in this study.  We will tell you 
what the results mean, how to find care, how to avoid infecting others, how we report 
HIV infection, and the importance of informing your partners at possible risk because 
of your HIV infection.
You will also be asked to co-enroll on the Surgical Oncology Program’s tissue collection protocol 
13C0176 (“Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or 
Surgical Resection of Solid Tumors”). 
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PATIENT IDENTIFICATION
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You will be removed from the study if you are found to be not eligible. 
During the Study
Before you begin treatment, you may have the following tests and/or procedures.  Some of these 
have already been explained at the beginning of this document:
Laparoscopy: 
This is an exploratory surgical procedure that allows us to examine inside of the abdomen, 
so we can see how much your cancer has spread. You will be given general anesthesia (so 
that you sleep through the surgery) and will undergo an abdominal operation requiring an 
incision. General anesthesia may be given through an IV (intravenous catheter, a small 
plastic tube that is put into a vein, usually in your arm), a face mask, or through a tube in 
your nose or throat. The general anesthesia may make it difficult to think once you wake 
up after your surgery, but this is temporary. However, because a side effect of general 
anesthesia is that it may take longer to fully recover then it will feel like at the time, you 
should plan ahead of time not to make any important decisions for 24 hours after the 
operation has been completed.
The surgeon will make a small incision in your abdominal wall and insert a lighted camera 
into your abdominal cavity.  The surgeon may also take small pieces of tissue, called 
biopsies, and fluid while examining the inside of your abdomen to check for tumors. If 
there is any leftover tissue after we have examined the biopsy sample to help us see if your 
cancer has spread, we may use the tissue for research purposes.  You’ll be admitted to the 
hospital to receive this procedure and you will be discharged a day later. 
Intraperitoneal (IP) Port Placement: 
During the laparoscopy, you will have an Intraperitoneal (IP) port inserted. This is what 
we will use to deliver the paclitaxel into your abdomen.  We will remove the port and 
catheter at the end of the study or if you stop participating for any reason.
Esophagogastroduodenoscopy (EGD): 
This is a test to examine the lining of your esophagus, stomach and the first part of your 
small intestine. You will receive this procedure only if your doctor decides that you need 
this test. A long, flexible tube with a camera on the end will be inserted through your mouth 
and into your stomach. This tube will be used to collect tissue samples from the lining of 
your stomach. We will apply a numbing agent to the back of your throat to reduce your 
discomfort and give you a medication to make you drowsy. Most people sleep through this 
procedure.
First Course of Study Treatment 
Paclitaxel 
You will receive the paclitaxel both through the IP port into your abdomen and through a regular 
IV into a vein on the first day of Week 1, Week 4 and Week 7. The treatment will be given in the 
outpatient center or on an inpatient unit and will last for about 4-6 hours. During this time, routine 
care such as vital signs, blood tests, and scans will be done if your study doctor thinks you need 
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them.  For 2 hours after the paclitaxel is infused into your abdomen, you will be instructed to 
change your position every 15 minutes.
Capecitabine 
Please take this drug for the first 14 days of the 21-day cycle by mouth twice a day and swallow it 
whole with water. You will not take this drug during the last 7 days of the 21-day cycle. You will 
be given a pill diary to take notes of your capecitabine intake.
After One Course (Three Cycles) of Treatment are Complete 
After you complete one course of treatment (i.e., 3 cycles for a total of 9 weeks), we will perform 
CT/PET Scans and laparoscopy to see how you are doing and if your cancer has responded to 
treatment. During your laparoscopy we will also perform another biopsy from inside of your 
abdomen. We may use any leftover biopsy tissue for research purposes. Some abdominal fluid 
may also be collected for research purposes. 
If your cancer has shrunk or has stayed the same, we will give you another course of treatment. 
If your cancer has worsened, we will not give you any more treatment.
Second Course of Study Treatment
The second course consists of three more cycles (9 weeks) of paclitaxel and capecitabine given in 
the same manner as in the first course. During this time, routine care such as vital signs, blood 
tests, and scans will be done if your doctor thinks you need them.
After you complete the second course of treatment, we will perform CT/PET scans and 
laparoscopy again to see how you are doing and how the cancer has responded to the treatment. 
Additional Research Testing
Quality of Life Questionnaire
You will be asked to complete Quality of Life questionnaires assessing your general well-being 
and function for research purposes throughout the study at the following times: once prior to your 
first course of study treatment, at the end of each treatment course you complete, and at each post-
treatment clinical visit. It will take about 30 minutes to complete the questionnaire and will only 
be done if you can complete the survey in English. 
If at any time you no longer want to complete the questionnaire you may do so. Your decision to 
participate or not to participate in completing the questionnaire will not have an effect on your 
treatment in the study. 
Research Samples
We will collect samples (blood, abdominal fluid and tissue) from you for research purposes only 
on this study. Blood samples may be collected from you for research purposes prior to your first 
course of study treatment (~2 teaspoons), once during Week 3 (~1.5 teaspoons) and again during 
Week 6 (~1.5 teaspoons), and at the end of each treatment course you complete (~1.5 teaspoons). 
On the day you receive paclitaxel, we will take multiple samples over the course of 24 hours (~2.5 
tablespoons total) starting from just before you receive the study drug.
Blood samples collected from you for research purposes will be used to study:
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The impact of the study treatment on your cancer and how it changes your tumors and 
your immune response.
How the genes in your DNA help the treatment drugs to transport, target and attack 
your tumors.
How your body processes the paclitaxel you are given.
Tumor tissue and abdominal fluid collected from you during your procedures will be used for 
research in order to:
Determine how much of the study treatment has reached and accumulated in your 
tumors and what genetic changes the treatment has made in your tumor tissue and 
immune response.
Identify the biomarkers associated with cancer cell progression to understand the 
molecular mechanisms of tumor development, growth, and response to treatment.
Identify if the study treatment is effectively destroying your cancer.
All of your samples collected for research purposes on this study may be used to look for specific 
changes in the DNA in tumors that could be used to develop new ways of diagnosing and treating 
cancer. DNA (also called deoxyribonucleic acid) in the cells carries genetic information and passes 
it from one generation of cells to the next – like an instruction manual. Normal tissue contains the 
DNA (instructions) that you were born with, DNA in tumor cells has changed – or mutated – and 
we think that change in the DNA is what causes tumors to form and to grow.  RNA (also called 
ribonucleic acid) carries the instructions from the DNA to the parts of your cells that make proteins.
To look at your DNA, we may do what is called “DNA sequencing.”  This is where we will do 
special tests in the lab to look at the sequence, or order, of how your DNA is put together.  This is 
what makes you unique.  
To determine which parts of the DNA have mutated, we will compare the DNA in your tumor cells 
to DNA from your normal cells. We will then analyze the results from similar tumors to see if 
there are any changes in the DNA that are common to a particular type of tumor.
However, you should know that the analyses that we perform in our laboratory are for research 
purposes only; they are not nearly as sensitive as the tests that are performed in a laboratory that 
is certified to perform genetic testing or testing for routine clinical care. For these reasons, we will 
not give you the results of the research tests done on your research samples in most cases.  There 
may be exceptions to what we share with you and this is described later in this consent form in the 
section for “Return of Research Results”.
HOW LONG WILL THE STUDY TAKE?
End of Treatment Visit
After therapy is stopped, we would like to see you for a safety visit 30 days after your last dose of 
study drug. This visit will take about 8 hours.
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Long-Term Follow-Up
After you finish the end of treatment visit described above, you will return to the NIH 3 months 
after the last dose of drug; then every 3 months for the first 2 years. After that, you will return 
every 6 months for the Years 3-5, and then every 6 months or yearly after 5 years (detailed below). 
Follow up visits may vary +/- 2 weeks for the first 2 years, and +/- 4 weeks thereafter. 
Your follow-up visit will include physical exam, dietary assessment, labs, scans and Quality of 
Life questionnaire (for 5 years only) and each visit will take about 8 hours. It will take about 30 
minutes to complete the questionnaire and will only be done if you can complete the survey in 
English.
If you are unable to come to NIH for your follow-up visit, you may visit your local physician for 
follow-up every 3 months for the first 2 years, every 6 months for Years 3-5 and then yearly, if 
felt to be appropriate by your study doctor. We may arrange for you to have certain needed tests 
done at outside labs for your follow-up, which may include scans to assess your disease and an 
electronic version of the questionnaire for our research. We may ask that you send the test results 
completed for your follow-up to us for our records. After your visit we would like to continue to 
touch base with you to check on how you are doing, either here at the Clinical Center or by phone 
or secure videocall/other NIH approved remote platform. 
After 5 years, if you are not able to come to NIH (and no longer want to complete follow-up visits 
with your local physician for this study) we may contact you, for the rest of your life, to see how 
you are doing and if you started new cancer treatment. If your cancer did not respond to the therapy, 
or if at any time you let us know that you no longer want to return to the NIH or see your local 
physician for study visits, you will not need to return. Instead we will contact you by phone or 
videocall/other NIH approved remote platform to see how you are doing and if you started new 
cancer treatment. 
HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY?
Approximately 74 people will participate in this study at the NIH. 
WHAT ARE THE RISKS AND DISCOMFORTS OF BEING IN THE STUDY?
There are risks, discomforts, and inconveniences associated with any research study. These 
deserve careful thought. You should talk with the study doctor if you have any questions.
It is probable that you will experience some of the side effects listed below, but it is unlikely that 
you will experience all of them. You will be watched closely, and we will give you medicines to 
try and prevent or reverse the side effects.  However, doctors don’t know all the side effects that 
may happen. Side effects may be mild or very serious.  In some cases, side effects can be serious, 
long lasting, or may never go away. We will tell you if we learn any new information that may 
affect your health, welfare, or decision to stay in this study. You should talk to your study doctor 
about any side effects that you have while taking part in the study.
IRB NUMBER: 19C0129
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Risks Associated with Paclitaxel
COMMON, SOME MAY BE SERIOUS
In 100 people receiving Paclitaxel, more than 20 and up to 100 may have:
Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat
Decrease in white blood cells which increases risk of infection
Infection, especially when white blood cell count is low
Bruising, bleeding
Anemia which may cause tiredness, or may require blood transfusions
Pain
Sores in mouth which may cause difficulty swallowing
Diarrhea, nausea, vomiting
Muscle weakness
Numbness, tingling or pain of the arms and legs
Hair loss
OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Paclitaxel, from 4 to 20 may have:
Abnormal heartbeat
Blood clot which may cause swelling, pain, shortness of breath 
Damage to the lungs which may cause shortness of breath
RARE, AND SERIOUS
In 100 people receiving Paclitaxel, 3 or fewer may have:
Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and 
tiredness
A tear or a hole in the bowels which may cause pain or that may require surgery
Severe skin rash with blisters and peeling which can involve mouth and other parts of the 
body
Risks Associated with Capecitabine
COMMON, SOME MAY BE SERIOUS
In 100 people receiving Capecitabine, more than 20 and up to 100 may have:
Swelling of the body
Blisters on the skin
Redness, pain or peeling of palms and soles
Pain
Diarrhea, loss of appetite, nausea, vomiting
Sores in mouth which may cause difficulty swallowing
Anemia which may require blood transfusions
Infection, especially when white blood cell count is low
Bruising, bleeding
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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COMMON, SOME MAY BE SERIOUS
In 100 people receiving Capecitabine, more than 20 and up to 100 may have:
Feeling of "pins and needles" in arms and legs
Tiredness
Fever
OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving Capecitabine, from 4 to 20 may have:
Blurred vision, dry or itchy eyes
Muscle spasms, body aches
Abnormal heartbeat
Restlessness, irritability
Swelling of face, fingers and lower legs
Dehydration, that when severe may lead to kidney damage
Constipation
Difficulty with balancing
RARE, AND SERIOUS
In 100 people receiving Capecitabine, 3 or fewer may have:
Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of 
breath, swelling of the face or throat
Difficulty speaking, walking or seeing
Internal bleeding which may cause blood in vomit or black tarry stools
Damage to the heart
Risks of Study Procedures
Blood Draws
Risks include temporary discomfort, pain, redness, bleeding, bruising, and swelling at the site
where the needle is inserted, and/or very rarely inflammation/infection of the vein, which could
require antibiotics. You may also experience dizziness, nausea, or rarely, fainting during blood
taking. Please tell the study doctor if you do not feel well after having your blood drawn.
Risks from Biopsy 
This procedure usually causes only brief discomfort at the site from which the biopsy is taken. 
Rarely, infection or bleeding may occur at the needle site. If received, the most common risks of 
conscious sedation last up to a few hours after being given and can include drowsiness, feeling 
slow or sluggish, low blood pressure, headache, and nausea. Tumor biopsy will be done by a 
specialist using the CT scanner or ultrasound to guide the biopsy needle into the tumor to ensure 
accuracy. We will give you more information about the risks of radiation during the CT guided 
biopsies on this study in this consent form below.
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 06/01/2022
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
General Anesthesia
Risks of general anesthesia include temporary confusion and memory loss, although this is more 
common in the elderly, dizziness, difficulty passing urine, bruising or soreness from the IV drip, 
nausea and vomiting, shivering and feeling cold, sore throat due to the breathing tube.
Electrocardiogram (EKG)
This test evaluates your heart rate and rhythm by measuring electrical impulses from the heart 
through electrodes that are placed on the skin.  You must lie down and be still without talking 
during the 5 minutes the EKG is being recorded. This procedure is associated with minimal 
discomfort.
Questionnaire 
The questionnaire may contain questions that are sensitive in nature. You are asked to only answer 
questions that you are comfortable with.
Scans and Contrast
CT and PET scans are common standard imaging tests used in the diagnosis of cancer. The most 
common discomfort is the length of time a patient must lay still during a scan. Occasionally, a 
patient may become uncomfortable with the closed space of the machines. If this occurs, your 
doctor can order a medicine to help you relax during this scan. If a contrast agent (the special dye) 
is given with the scan there is a small risk of having a reaction to the contrast. In that small group 
of patients who have a reaction, the most common symptoms are nausea, pain in the vein where 
the contrast was given, a metallic or bitter taste in the mouth, and a warm or flushing feeling that 
lasts from 1-3 minutes. Rarely do these symptoms require any treatment. In very rare cases, people 
have had severe reactions that affect their breathing and heart rhythm. If you have had a reaction 
in the past, be sure to tell you doctor or nurse about it. 
An IV catheter may need to be inserted for administration of the contrast agent or anesthetic.  This 
can cause pain at the site where the IV is placed and carries a small risk of bruising or infection, 
or inflammation of the skin and vein with pain and swelling.
For oral contrast: You may experience vomiting, nausea, cramping, bloating, constipation or 
diarrhea after drinking the contrast.
What are the risks of radiation from being in the study? 
During your participation in this research study, you will be exposed to radiation from 6 PET/CT 
scans as well as 3 CT-guided biopsies over the course of the first year. The amount of radiation 
exposure you will receive from these procedures is equal to approximately 9.6 rem. A rem is a unit 
of absorbed radiation.  
Every day, people are exposed to low levels of radiation that come from the sun and the 
environment around them.  The average person in the United States receives a radiation exposure 
of 0.3 rem per year from these sources.  This type of radiation is called “background radiation.”  
No one knows for sure whether exposure to these low amounts of radiation is harmful to your 
body. 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
The CT scans, PET/CT scans and CT-guided biopsies that you get in this study will expose you to 
the roughly the same amount of radiation as 32.0 years’ worth of background radiation. Being 
exposed to too much radiation can cause harmful side effects such as an increase in the risk of 
cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 
40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die 
from cancer. The risk of getting cancer from the radiation exposure in this study is 1.0 out of 100 
(1.0%) and of getting a fatal cancer is 0.5 out of 100 (0.5%).
You may not participate in this study if you are pregnant. If you are capable of becoming pregnant, 
we will perform a pregnancy test before exposing you to radiation. You must tell us if you may 
have become pregnant within the previous 14 days because the pregnancy test is unreliable during 
that time.
Esophagogastroduodenoscopy (EGD) 

Slowing of breathing and abnormal heart rhythms from the medications used to make you 
drowsy.

A tear in your digestive track – these are rare (3 in every 10,000 procedures) and are 
treated with antibiotics.

Fever, ulcers, serious infection and scarring and narrowing of the esophagus.

Bleeding from the GI tract.

The contents of your stomach may be breathed into your lungs.

Allergic reaction to the drugs given during the procedure.
Risks of Intraperitoneal Port Insertion
Intraperitoneal Port Insertion is a minimally-invasive procedure. The risks from this procedure and 
general anesthesia include:

Pain

Infection at the area of insertion or inside the abdomen.

Rarely, the port may become blocked, displaced, or stop working and require a procedure 
to fix or replace it.
Risks of Laparoscopy
Laparoscopy is minor surgery. The risks from these operations, in addition to the risks of general 
anesthesia include: 

Pain 

Temporary slowing or stopping of bowel function, known as an ileus. This could take 
several days to resolve and may require that the tube in your nose that drains your stomach 
stay in place longer.

This surgery may also cause changes in your bowel pattern, either constipation or diarrhea.  
Fluid may develop in your abdomen, known as ascites. This may go away on its own or 
may need to be drained if it becomes too uncomfortable.
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 06/01/2022
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY

Rarely, this surgery may cause injury to organs in the abdomen such as the intestines, 
stomach, bladder and blood vessels. If this occurs you may require prolonged 
hospitalization or additional surgery.

There may be an increased risk of wound healing or infection after this surgery because of 
the use of paclitaxel and capecitabine.
What are the Risks Related to Pregnancy? 
If you are capable of becoming pregnant, we will ask you to have a pregnancy test before beginning 
this study. You will need to practice an effective form of birth control before starting study 
treatment, during study treatment, and for 3 months after you finish study treatment (the restricted 
period). If you become pregnant, there may be unknown risks to the fetus or unborn child, or risks 
that we did not anticipate. There may be long-term effects of the treatment being studied that could 
increase the risk of harm to a fetus. You must tell the study doctor if your birth control method 
fails during the restricted period. If you think or know you have become pregnant during the 
restricted period, please contact the research team member identified at the top of this document 
as soon as possible. 
If you are a sexually active person with a partner capable of becoming pregnant, it is important 
that your partner not become pregnant during the restricted period. There may be unknown risks 
to a fetus or risks we did not anticipate. You and your partner must agree to use birth control if 
you want to take part in this study. If you think your partner has become pregnant during the 
restricted period, please contact the research team member identified at the top of this document 
as soon as possible.  If you and your partner plan for your partner to become pregnant after the 
restricted period, please discuss this with the study team.
Privacy Risks Associated with Genetic Testing
It may be possible that genetic information from you could be used by law enforcement agencies 
or other entities to identify you or your blood relatives.
Psychological or Social Risks Associated with Return of Incidental or Secondary Findings
As part of the research study, it is possible that you could learn that you have genetic risks for 
another disease or disability. This may be upsetting and, depending on what you learn, might create 
a need to make challenging decisions about how to respond. 
Although your genomic information is unique to you, you share some genomic similarities with 
your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your 
research results could mean something about your family members and might cause you or your 
family distress. Before joining the study, it may be beneficial to talk with your family members 
about whether and how they want you to share your results with them. 
Protections Against Misuse of Genetic Information 
This study involves genetic testing on samples.  Some genetic information can help predict future 
health problems of you and your family and this information might be of interest to your employers 
or insurers. The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits 
plans and health insurers from requesting genetic information or using genetic information. It also 
prohibits employment discrimination based on your health information.  However, GINA does not 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 06/01/2022
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
address discrimination by companies that sell life insurance, disability insurance, or long-term care 
insurance. GINA also does not protect you against discrimination based on an already-diagnosed 
genetic condition or disease that has a genetic component.
WHAT ARE THE BENEFITS OF BEING IN THE STUDY?
You might not benefit from being in this study. 
However, the potential benefit to you might be shrinking of your tumor or decrease in your 
symptoms, such as pain, that are caused by the cancer.  Because there is not much information 
about the drug’s effect on your cancer, we do not know if you will benefit from taking part in this 
study.
Are there any potential benefits to others that might result from the study?
In the future, other people might benefit from this study because what we learn in this study may 
eventually be used to treat others with your disease. 
WHAT OTHER OPTIONS ARE THERE FOR YOU?
Instead of being in this study, you have these options:

Choose to be treated with surgery, radiation or with other chemotherapy drugs. 

Choose to take part in a different study, if one is available.

Choose not to be treated for cancer and instead receive comfort care to relieve symptoms.
You should discuss with your doctor your other choices and their risks and benefits.
DISCUSSION OF FINDINGS
New Information About the Study
If we find out any new information that may affect your choice to participate in this study, we 
will get in touch with you to explain what we have learned. This may be information we have 
learned while doing this study here at the NIH or information we have learned from other 
scientists doing similar research in other places.
Return of Research Results
When we are examining your DNA, it is possible that we could identify possible changes in other 
parts of your DNA that are not related to this research. These are known as “incidental medical 
findings”. 
These include: 

Changes in genes that are related to diseases other than cancer 

Changes in genes that are not known to cause any disease. These are known as normal 
variations. 

Changes in genes that are new and of uncertain clinical importance. This means that we do 
not know if they could cause or contribute to a disease or if they are normal variations. 
Since the analyses that we perform in our laboratory are not nearly as sensitive as the tests that 
are performed in a laboratory that is certified to perform genetic testing, the genetic changes that 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
we find may or may not be valid.  Therefore, we do not plan to inform you of all of the genetic 
results of testing on your tissue and blood that is performed in our research lab. However, in the 
unlikely event that we discover a finding believed to be clinically important based on medical 
standards at the time we first analyze your results, we will contact you. This could be many years 
in the future. We will ask you to have an additional tube of blood drawn to verify the findings 
we have seen in our lab.
Once the results are available, we will offer to have you come to NIH (at our expense) to have 
genetic education and counseling to explain this result. 
If you do not want to come to NIH, we will help you find a local genetic healthcare provider 
who can explain it to you (at your expense).
If you are not contacted, you should not assume that that you do not have any gene variants that 
might be related to a disease. 
EARLY WITHDRAWAL FROM THE STUDY 
Your doctor may decide to stop your participation in the study for the following reasons:

if he/she believes that it is in your best interest

if your disease worsens or comes back during treatment

if you have side effects from the treatment that your doctor thinks are too severe

if new information shows that another treatment would be better for you

if you become pregnant

if you do not follow the study rules

if the study is stopped for any reason
In this case, you will be informed of the reason your participation is being stopped.
After therapy is stopped we would like to see you for a safety visit 30 days after your last dose. 
You can stop taking part in the study at any time. However, if you decide to stop taking part in the 
study, we would like you to talk to the study doctor and your regular doctor first.
If you decide at any time to withdraw your consent to participate in the trial, we will not collect 
any additional medical information about you.
STORAGE, SHARING AND FUTURE RESEARCH USING YOUR SPECIMENS AND 
DATA
Will Your Specimens or Data Be Saved for Use in Other Research Studies?
As part of this study, we are obtaining specimens and data from you. We will remove all the 
identifiers, such as your name, date of birth, address, or medical record number and label your 
specimens and data with a code so that you cannot easily be identified. However, the code will 
be linked through a key to information that can identify you. We plan to use these specimens and 
data for studies other than the ones described in this consent form that going on right now, as 
well as studies that may be conducted in the future. These studies may provide additional 
information that will be helpful in understanding stomach cancer or other diseases or conditions. 
This could include studies to develop other research tests, treatments, drugs, or devices, that may 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 06/01/2022
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
lead to development of a commercial product by the NIH and/or its research or commercial 
partners. There are no plans to provide financial compensation to you if this happens. Also, it is 
unlikely that we will learn anything from these studies that may directly benefit you. 
I give permission for my coded specimens and data to be stored and used for future research as 
described above.
_____ Yes
_____ No
Initials
Initials
Will Your Specimens or Data Be Shared for Use in Other Research Studies? 
We may share your coded specimens and data with other researchers. If we do, while we will 
maintain the code key, we will not share it, so the other researchers will not be able to identify 
you. They may be doing research in areas similar to this research or in other unrelated areas. 
These researchers may be at NIH, other research centers and institutions, or commercial entities.
I give permission for my coded specimens and data to be shared with other researchers and used 
by these researchers for future research as described above.
_____ Yes 
_____ No
Initials
Initials
If you change your mind and do not want us to store and use your data for future research, you 
should contact the research team member identified at the top of this document. We will do our 
best to comply with your request but cannot guarantee that we will always be able to destroy 
your data. For example, if some research with your data has already been completed, the 
information from that research may still be used. Also, for example, if the data have been shared 
already with other researchers, it might not be possible to withdraw them. 
In addition to the use and sharing of your data described above, we might remove any 
information from your data that can identify you such as name, address, or medical record 
number, and then use the data for additional research studies at the NIH or other places. If we do 
this, we might not contact you to ask your permission or otherwise inform you.
NIH policies require that your clinical and other study data be placed in an internal NIH database 
that is accessible to other NIH researchers for future research. These researchers will not have 
access to any of your identifiers, such as your name, date of birth, address, or medical record 
number; and your data will be labeled with only a code. We cannot offer you a choice of whether 
your data to be placed in this database or not.  If you do not wish to have your data placed in this 
database, you should not enroll in this study.  
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Will Your Genomic Data Be Shared Outside of This Study?
As part of this research study, we will put your genomic data in a large database for broad sharing 
with the research community. These databases are commonly called data repositories. The 
information in this database will include but is not limited to genetic information, race and 
ethnicity, and sex.  If your individual data are placed in one of these repositories, they will be 
labeled with a code and not with your name or other information that could be used to easily 
identify you, and only qualified researchers will be able to access them. These researchers must 
receive prior approval from individuals or committees with authority to determine whether these 
researchers can access the data.
Summary information about all of the participants included in this study (including you) is being 
placed in a database and will be available through open access. That means that  researchers and 
non-researchers will be able to access summary information about all the participants included in 
the study, or summary information combined from multiple studies, without applying for 
permission. The risk of anyone identifying you with this information is very low.
As part of this study, we will put your genomic data in a large database which will be freely 
available to the public. These databases are commonly called data repositories. These data are 
intended for other researchers to use and learn from but anyone can gain access to them, including 
law enforcement. The information in this database will include but is not limited to genetic 
information, race, ethnicity and sex.  If your individual data are placed in one of these repositories, 
they will be labeled with a code and not with your name or other information that could be used to 
easily identify you.  This information when combined with information from other public sources 
could be used to identify you, though we believe it is unlikely that this will happen.
NIH policies require that genomic data be placed in a repository for sharing. Therefore, we 
cannot offer you a choice of whether your data will be shared.  If you do not wish to have your 
data placed in a repository, you should not enroll in this study.  
How Long Will Your Data be Stored by the NIH?
Your specimens and data will be stored at NIH indefinitely. 
Risks of Storage and Sharing of Specimens and Data
When we store your specimens and data, we take precautions to protect your information from 
others that should not have access to it. When we share your data, we will do everything we can 
to protect your identity, for example, when appropriate, we remove information that can identify 
you. Even with the safeguards we put in place, we cannot guarantee that your identity will never 
become known or someone may gain unauthorized access to your information. New methods may 
be created in the future that could make it possible to re-identify your specimens and data. 
COMPENSATION, REIMBURSEMENT, AND PAYMENT
Will I receive compensation for participation in the study?
Some NIH Clinical Center studies offer compensation for participation in research. The amount 
of compensation, if any, is guided by NIH policies and guidelines.
You will not receive compensation for participation in this study. 
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Will I receive reimbursement or direct payment by NIH as part of my participation?
Some NIH Clinical Center studies offer reimbursement or payment for travel, lodging or meals 
while participating in the research. The amount, if any, is guided by NIH policies and guidelines.
The NCI generally does not cover expenses during screening.  If you are scheduled for and begin 
treatment the NCI will cover the cost for some of your expenses. Some of these costs may be paid 
directly by the NIH and some may be reimbursed after you have paid.  Someone will work with 
you to provide more information.
Will taking part in this research study cost me anything? 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 

If some tests and procedures are performed outside the NIH Clinical Center, 
you may have to pay for these costs if they are not covered by your insurance 
company.

Medicines that are not part of the study treatment may not be provided or paid 
for by the NIH Clinical Center.

Once you have completed taking part in the study, medical care will no longer be 
provided by the NIH Clinical Center.
CONFLICT OF INTEREST(COI) 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a COI Guide.  You may ask your research team for a copy 
of the COI Guide or for more information.  Members of the research team who do not work for 
NIH are expected to follow these guidelines or the guidelines of their home institution, but they 
do not need to report their personal finances to the NIH.
No NIH investigator involved in this study receives payments or other benefits from any 
company whose drug, product or device is being tested.
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Some of your health information, and/or information about your data, from this study will be 
kept in a central database for research. Your name or contact information will not be put in the 
database. Your test results will be identified by a unique code and the list that links the code to 
your name will be kept separate from your data and health information. Your information may 
be given out if required by law. For example, certain states require doctors to report to health 
boards if they find a disease like tuberculosis. However, the researchers will do their best to 
make sure that any information that is released will not identify you.
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy. Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The National Cancer Institute and other government agencies, like the Food and Drug 
Administration (FDA), which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board 
When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified.  In most cases, the NIH will not release any 
information about your research involvement without your written permission.  However, if you 
sign a release of information form, for example, for an insurance company, the NIH will give the 
insurance company information from your medical record.  This information might affect (either 
favorably or unfavorably) the willingness of the insurance company to sell you insurance.
If we share your specimens or data with other researchers, in most circumstances we will remove 
your identifiers before sharing your specimens or data. You should be aware that there is a slight 
possibility that someone could figure out the information is about you. 
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
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CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical records we 
collect under the authority of the Public Health Service Act.  In some cases, the Privacy Act 
protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy Act 
allows release of information from your medical record without your permission, for example, if 
it is requested by Congress. Information may also be released for certain research purposes with 
due consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Dr. Jeremy L. 
Davis at 240-858-3731 or jeremy.davis@nih.gov. You may also call the NIH Clinical Center 
Patient Representative at 301-496-2626, or the NIH Office of IRB Operations at 301-402-3713, if 
you have a research-related complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
IRB NUMBER: 19C0129
IRB APPROVAL DATE: 07/05/2022


PATIENT IDENTIFICATION
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.
IRB NUMBER: 19C0129
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Prot_SAP_002.pdf: 
Abbreviated Title: IP and IV Paclitaxel for GC
Version Date:06/01/2022
1
Abbreviated Title: IP and IV Paclitaxel for GC
NIH Protocol #: 19C0129 
Version Date: 06/01/2022
NCT Number #: NCT04034251
Title: A Phase II Study of Intraperitoneal and Intravenous Paclitaxel Chemotherapy with Oral 
Capecitabine for Gastric Adenocarcinoma with Peritoneal Carcinomatosis
NCI Principal Investigator:
Jeremy L. Davis, MD
Surgical Oncology Program (SOP), CCR, NCI, NIH
Building 10, Room 4-3760
10 Center Drive
Bethesda, MD 20892
Phone: 240-858-3731
E-mail: jeremy.davis@nih.gov
Investigational Agents: None
Commercial Agents: Paclitaxel (Taxol®), Capecitabine (Xeloda®) 
Commercial Device: BardPort Titanium Implanted Port with Peritoneal Catheter


Abbreviated Title: IP and IV Paclitaxel for GC
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2
PRÉCIS
Background:

An estimated 28,000 cases of gastric adenocarcinoma are diagnosed annually in the 
U.S.

Peritoneal metastasis is a common finding at diagnosis, making curative surgical 
resection possible in an estimated 25% of patients.

Systemic chemotherapy is the recommended treatment for patients with metastatic 
gastric cancer to the peritoneal cavity, however selective use of cytoreductive surgery 
and intraperitoneal chemotherapy has been associated with improved overall survival. 

Multiple chemotherapeutic agents and delivery systems have been described for 
intraperitoneal therapy, but no standard regimen exists. 
Objective:

Determine the progression free survival (PFS) in patients with peritoneal metastases 
from gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) 
and systemic paclitaxel administration with concomitant capecitabine therapy.
Eligibility:

Histologically confirmed adenocarcinoma of the stomach.

Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence 
of peritoneal carcinomatosis found at staging laparoscopy.

Medically fit for systemic chemotherapy and intraperitoneal chemotherapy.

Men and women age ≥ 18 years.  
Design:

Phase II, nonrandomized, open label study. 

Patients will enroll in two cohorts: those with prior systemic chemotherapy and those 
who are treatment naïve.  

Patients will undergo staging laparoscopy and placement of peritoneal access port.  

Intraperitoneal paclitaxel (60 mg/m2 weekly), intravenous paclitaxel (80 mg/m2 
weekly), and capecitabine (825 mg/m2 twice daily for 14 days of each cycle) for 12 
weeks.

Treatment response will be assessed with imaging and laparoscopy.

It is expected that 16-20 patients per year for total 4 years will be enrolled. The accrual 
ceiling is set at 74 patients. 


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TABLE OF CONTENTS 
PRÉCIS............................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................3
STATEMENT OF COMPLIANCE ................................................................................................5
1
INTRODUCTION ...................................................................................................................5
1.1
Study Objectives ...............................................................................................................5
1.2
Background and Rationale................................................................................................6
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................15
2.1
Eligibility Criteria ...........................................................................................................15
2.2
Screening Evaluation ......................................................................................................16
2.3
Participant Registration and Status Update Procedures..................................................18
2.4
Baseline Evaluation.........................................................................................................19
3
STUDY IMPLEMENTATION .............................................................................................19
3.1
Study Design...................................................................................................................19
3.2
Drug Administration .......................................................................................................21
3.3
Dose Modifications.........................................................................................................22
3.4
Subcutaneous Infusion Port Complications ....................................................................25
3.5
Study Calendar................................................................................................................26
3.6
Surgical Guidelines.........................................................................................................29
3.7
Cost and Compensation ..................................................................................................31
3.8
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................32
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................33
5
CORRELATIVE STUDIES ..................................................................................................33
5.1
Biospecimen Collection Table........................................................................................33
5.2
Sample Collection and Processing..................................................................................34
5.3
Sample Storage, Tracking and Disposition.....................................................................35
6
DATA COLLECTION AND EVALUATION .....................................................................38
6.1
Data Collection ...............................................................................................................38
6.2
Data Sharing Plans..........................................................................................................40
6.3
Response Criteria ............................................................................................................41
6.4
Toxicity Criteria..............................................................................................................43
7
NIH REPORTING REQUIREMENTS/DATA SAFETY MONITORING PLAN ..............44


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7.1
Definitions.......................................................................................................................44
7.2
OHSRP Office of Compliance and Training/IRB Reporting..........................................44
7.3
NCI Clinical Director Reporting.....................................................................................44
7.4
NIH Required Data and Safety Monitoring Plan............................................................44
8
STATISTICAL CONSIDERATIONS ..................................................................................45
8.1
Statistical Hypotheses .....................................................................................................45
8.2
Sample Size Determination.............................................................................................45
8.3
Populations for Analyses ................................................................................................46
8.4
Statistical Analyses .........................................................................................................46
9
HUMAN SUBJECTS PROTECTIONS................................................................................48
9.1
Rationale for Subject Selection.......................................................................................48
9.2
Participation of Children.................................................................................................48
9.3
Participation of Subjects Unable to Give Consent..........................................................48
9.4
Evaluation of Benefits and Risks/Discomforts ...............................................................48
9.5
Consent Process and Documentation..............................................................................50
10
REGULATORY AND OPERATIONAL CONSIDERATIONS..........................................52
10.1
Study Discontinuation and Closure.................................................................................52
10.2
Quality Assurance and Quality Control..........................................................................52
10.3
Conflict of Interest Policy...............................................................................................52
10.4
Confidentiality and Privacy ............................................................................................53
11
PHARMACEUTICAL AND INVESTIGATIONAL DEVICE INFORMATION...............53
11.1
Paclitaxel (Taxol®)..........................................................................................................54
11.2
Capecitabine (Xeloda®)...................................................................................................55
11.3
Subcutaneous Intraperitoneal Infusion Port....................................................................56
12
REFERENCES ......................................................................................................................58
13
APPENDICES .......................................................................................................................61
13.1
Appendix A: Performance Status Criteria ......................................................................61
13.2
Appendix B: CARCINOMATOSIS EXTENT EVALUATION....................................62
13.3
Appendix C: Oral Medication Diary...............................................................................63
13.4
Appendix D: General Specimen Collection Reference (Refer to Official Timepoints in 
Protocol 13C0176).....................................................................................................................64


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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.
1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective

Determine the progression free survival (PFS) in patients with peritoneal metastases from 
gastric cancer after repeated intraperitoneal chemotherapeutic infusion (IPC) and systemic 
paclitaxel administration with concomitant capecitabine therapy. 
1.1.2
Secondary Objectives

Determine intra-peritoneal progression free survival (iPFS).  

Determine distant (extra-peritoneal) disease free survival.

Determine the frequency of objective histopathologic response to therapy. 

Describe the morbidity of this treatment strategy.

Determine overall survival.
1.1.3
Exploratory Objectives

Evaluate the impact of repeated intraperitoneal chemotherapeutic infusion (IPC) and 
systemic paclitaxel administration with concomitant capecitabine therapy on circulating 
tumor cells and immune subsets.     

Determine the pharmacokinetics of repeated intraperitoneal chemotherapeutic infusion 
(IPC) and systemic paclitaxel administration with concomitant capecitabine therapy in 
patients with peritoneal metastases from gastric cancer.

Evaluate the genomic DNA and genotype in patients with peritoneal metastases from 
gastric cancer in order to determine the most relevant drug metabolizing enzymes and 
transporters (DMET) through pharmacogenetic analyses.

Define the risk of developing peritoneal metastasis in gastric cancer, and other associated 
cancers, through genotype/phenotype correlations.


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
Determine the molecular changes and mechanisms of tumor initiation, invasion and 
metastasis in gastric cancers with peritoneal metastasis.

Evaluate chemotherapeutic and immunotherapeutic agent effects of systemic paclitaxel 
administration with concomitant capecitabine therapy in patients with peritoneal 
metastases from gastric cancer using a novel ex-vivo platform, the SMART System.
1.2
BACKGROUND AND RATIONALE
1.2.1
Study Disease
Worldwide, gastric cancer remains a global health concern given the nearly 1 million new 
diagnoses made annually. Of those diagnosed, three quarters of patients will die of their disease 
making gastric cancer the third most common cause of cancer-related death.[1] Survival at 5-years 
remains a dismal 33%, with a median survival of approximately 12 months for patients with stage 
IV disease.[2, 3] While systemic chemotherapy can extend survival for patients, only surgical 
resection offers the chance for cure. Unfortunately, only 25% of newly diagnosed patients with 
gastric cancer are eligible for resection due to metastatic disease at presentation.[4] 
A major barrier to successful surgery in gastric cancer is its propensity for peritoneal metastasis. 
Metastases range from microscopic (i.e., positive cytology) to overt tumor nodules and omental 
caking. Moreover, diagnosis of peritoneal carcinomatosis is challenging as non-invasive modes of 
identification are insensitive. As such, laparoscopic staging is recommended for newly diagnosed 
patients without radiographic evidence of metastases. In addition to visual inspection at 
laparoscopy, in nearly 20% of cases, peritoneal washings with cytopathologic examination will 
identify microscopic peritoneal disease.[5] Thus, the addition of staging laparoscopy and 
peritoneal cytology can prevent non-curative laparotomy in 23-31% of patients considered 
surgically resectable due to no radiographic evidence of metastasis.[6, 7] 
To address the unique problem of peritoneal metastasis, cytoreductive surgery (CRS) and 
hyperthermic intraperitoneal chemotherapy (HIPEC) has been evaluated in several studies 
attempting to establish this technique as a treatment strategy for gastric cancer. Unfortunately, the 
lack of standardization across studies and the failure to reproduce positive results have left the 
purported benefit of CRS/HIPEC in question.[8] In studies where a survival advantage has been 
shown, it was primarily in patients with low disease burden and when complete resection could be 
achieved.[9] For patients in whom complete macroscopic resection cannot be achieved, systemic 
chemotherapy remains first-line therapy. Our branch has an open treatment protocol (17C0070; 
HIPEC for Gastric Cancer) for patients with gastric cancer and limited peritoneal carcinomatosis. 
Patients with low peritoneal cancer index (PCI ≤ 10) who have received a minimum of 3 months 
of systemic chemotherapy are eligible for treatment with gastrectomy, cytoreduction and HIPEC. 
As of August 15, 2018, twelve patients have been enrolled and treated. The median PCI at time of 
study enrollment was 5. Although this low PCI portends a better prognosis, the median time to 
progression in the 5 of 12 patients with adequate follow-up is 6 months. While this study is 
ongoing, it highlights the severity of the disease and the urgent need for better therapy. Moreover, 
less than 50% of patients screened with laparoscopy for that trial (17C0070) have proven eligible 
based on a PCI greater than 10. 
Metastatic gastric cancer is commonly treated systemically with a fluoropyrimidine and platinum 
chemotherapeutic agents. This combination therapy has a modest median survival benefit of 1.6 
months compared to single agent therapy.[4] In patients with good performance status and limited 


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comorbidities, triple drug regimens that include a taxane have been shown to increase time to 
progression and overall survival.[10] The first successful targeted therapy of gastric cancer with 
trastuzumab for HER2-positive tumors conveyed a mere 2.7 month median overall survival 
advantage in the 20% of patients in which HER2 was overexpressed.[11] [12] Beyond first-line 
therapy, most second-line options are limited.[13] Although immune checkpoint inhibitors (e.g. 
anti-PD-L1) show great promise, few patients with peritoneal metastasis are eligible for 
immunotherapy. Based on the Keynote-059 study of pembrolizumab in patients with advanced 
gastric cancer, an impressive median overall survival of 20.7 months was demonstrated in patients 
with PD-L1-positive tumors. The most likely tumors to either express PD-L1 and/or respond to 
immune checkpoint inhibitors are EBV+ or microsatellite unstable (MSI-hi) tumors. Based on 
TCGA data in gastric adenocarcinoma, EBV+ and MSI gastric cancers are molecularly distinct 
from the so-called Genomically Stable (GS) molecular sub-type. Peritoneal metastasis is most 
likely to occur in the diffuse histologic subtype of gastric cancer, which makes up 70% of the GS 
molecular sub-group in the TCGA data set. In our own prospective analysis of patients with 
metastatic gastric adenocarcinoma (17C0044; Molecular Profiling of Gastric Tumors) we have re-
capitulated the TCGA findings by showing that gastric adenocarcinomas of the diffuse histologic 
subtype do not demonstrate PD-L1 positivity or microsatellite instability (MSI-hi, by 
immunohistochemical analysis) (data not shown).
1.2.2
Rationale for Regional Therapy in Gastric Cancer
With the limited efficacy of systemic chemotherapy and the inconsistent results of cytoreductive 
surgery, patients with peritoneal carcinomatosis have limited viable treatment options. One 
potential treatment strategy is normothermic intraperitoneal chemotherapy (without cytoreductive 
surgery). Intraperitoneal (IP) drug delivery is an effective treatment strategy in certain solid tumors 
prone to peritoneal carcinomatosis. The rationale for regional chemotherapy to the peritoneal 
surfaces is to maximize drug delivery to affected sites of disease while increasing the therapeutic 
window by limiting systemic toxicity. Work performed at NCI and elsewhere has established the 
pharmacokinetic rationale for IP drug delivery.[14-16] Subsequent clinical studies have 
established IP chemotherapy as the optimal treatment for patients with ovarian carcinomatosis, 
primary peritoneal mesothelioma and appendiceal mucinous neoplasms.[17-19] 
For intraperitoneal chemotherapy administration, taxanes are ideal agents given their high 
molecular weight and hydrophobic properties that allow for prolonged intraperitoneal 
retention.[20]  Taxanes are a class of cytotoxic chemotherapeutic agents that induce excessive 
polymerization of tubulin resulting in dysfunctional microtubules, which leads to mitotic arrest 
and subsequent cell death.[21]  In a review of intraperitoneal pharmacokinetics by Markman, 
paclitaxel was found to have the highest peak intraperitoneal concentration compared to other 
commonly used intraperitoneal agents.[22] When compared to cisplatin, the most common 
chemotherapeutic used for HIPEC, the peak concentration of paclitaxel was 50 times higher.[22]  
This high intraperitoneal concentration is believed to lead to its direct cytotoxic effects.  While 
concentrations can remain elevated as long as 72 hours after infusion[23], morphologic signs of 
cellular distress are noted just 6 hours after infusion.[24] Another challenge of intraperitoneal drug 
delivery is the complex network of microvasculature that supplies tumors.  It is hypothesized that 
increased blood supply enhances metabolic features of these cells and leads to increased 
proliferation and further metastatic spread.[25] This vast microvascular network is also 
hypothesized to contribute to the ineffectiveness of intravenous chemotherapeutics.  The purported 
mechanism for systemic therapy resistance is leakage of chemotherapeutic agents from the 


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8
vasculature of the tumor into the free peritoneal space.[25] In vitro experiments using human 
gastric cancer nodules have demonstrated that intraperitoneal paclitaxel was found to result in 
injury or collapse of tumor micro vessels. This angiogenic inhibition results in a layer of hypoxic 
cell death surrounding a far less metabolically active central tumor.[25]  We hypothesize that the 
coadministration of systemic chemotherapy can have an additive effect given the microvascular 
destruction and decreased likelihood of intraperitoneal leakage. 
Depth of tumor penetration by taxanes after a single dose is limited.  The two most commonly 
used taxanes, paclitaxel and docetaxel, have been directly compared in vitro.  In a study by Kyle 
et al, paclitaxel tumor invasion was found to be twice that of docetaxel but the majority of drug 
accumulated in the first 100 µm of tumor.[26]  In order to augment the limited penetration of a 
single dose, the utilization of peritoneal catheters has been employed for repeated dosing.  In early 
Phase I studies, the pharmacokinetic analysis and safety profile of paclitaxel has been established.  
Kodera et al, established a recommended dose of 60 mg/m2 with minimal toxicity when 
intraperitoneal paclitaxel was given as a single agent.  At this dose level, drug half-life ranged 
from 17.4-65.3 hours.[27]  Although peak intraperitoneal concentration was 7000 times higher 
than that of the plasma[28], some systemic absorption was expected.  Another Phase I study of 
combined intravenous and intraperitoneal paclitaxel established a recommended dose of 20 
mg/m2.[29]  Despite a one-third dose reduction of the intraperitoneal paclitaxel, the authors were 
able to demonstrate consistently high peak peritoneal concentration at both 48 and 72 hours after 
administration.[29] 
Clinical studies using intraperitoneal taxanes have shown good patient tolerance and limited 
systemic adverse events, even with concomitant intravenous administration (Table 1).[23, 27-31]  
In Phase I studies, anemia was the most common toxicity although the majority of these were 
Grade 2.[29]  In that same Phase I study, of the six patients that received 20 mg/m2, no Grade 5 
toxicity was seen and leukopenia and neutropenia were the only Grade 3 or 4 toxicities.[29]  In a 
subsequent Phase II study of 40 patients receiving both intraperitoneal and intravenous paclitaxel, 
the rate of Grade 3 and 4 adverse events were 40% and 15% respectively.[23]  The most common 
adverse events were neutropenia (38%), leukopenia (18%) and anemia (10%).[23]  Notably no 
patients experienced adverse effects related to intraperitoneal infusion such as abdominal pain or 
cramping.[23]  


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Table 1: Summary of Previous Intraperitoneal and Intravenous Paclitaxel Administration in Gastric 
Cancer
Intraperitoneal administration of paclitaxel has shown promising results in Phase I and II studies.  
When repeated intraperitoneal paclitaxel infusion was added to approved systemic chemotherapy 
regimens, tumor response rates greater than 50% were observed with associated median survival 
times of 22.6 and 17.6 months.[23, 31] Specifically, a Phase II study by Yamaguchi and colleagues 
evaluated IP paclitaxel combined with IV paclitaxel and oral S-1 chemotherapy in patients with 
macroscopic peritoneal metastases in patients with gastric cancer.[31] S-1 is a combination of three 
compounds (tegafur, gimeracil, oteracil potassium) developed as a replacement for infusional 5-
FU therapy. In that study, 35 patients were enrolled and evaluated for survival endpoints. The 1-
year survival was 77%, which compared favorably to approximately 50% 1-year survival in 
historical controls treated with systemic therapy alone. Moreover, in patients with measurable 
intraperitoneal disease, the objective response rate was 71% and positive peritoneal cytology 
resolved to negative in 97% (28 of 29) of patients. Although Yamaguchi et al. demonstrated safety 
and efficacy of IP and IV paclitaxel along with S-1, this oral 5-FU prodrug is not available in the 
United States. S-1 is combined with cisplatin and is standard systemic therapy for advanced gastric 
cancer in Japan. Similarly, 5-FU is combined with multiple cytotoxic chemotherapy agents for 
treatment of patients with gastric adenocarcinoma in the U.S. and other European nations.  
Importantly, investigators have observed that patients whose tumors do not respond to 
intraperitoneal chemotherapy do not appear to benefit from cytoreductive surgery.  Therefore, we 
propose using IP paclitaxel to aid in the identification of patients who may benefit from this 
treatment strategy of regional and systemic therapy.


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1.2.3
Drivers of Peritoneal Metastasis in Gastric Cancer 
Gastric adenocarcinoma is a heterogeneous disease with various environmental and genetic 
predisposing factors. Comprehensive molecular analyses published in recent years have provided 
additional insight into distinct sub-classifications of gastric cancer based on unique molecular 
alterations.[32, 33] These studies have revealed novel correlations of molecular subtypes with 
distinct tumor phenotypes and clinical outcomes.[33] Peritoneal carcinomatosis is a particularly 
morbid and common feature of gastric adenocarcinomas. The association between diffuse-type 
tumor histology and increased rates of carcinomatosis is well-documented.[34] Somatic gene 
alterations that impair E-cadherin protein expression are also a recurring feature of sporadic 
diffuse-type gastric cancers.[35] Germline mutation in CDH1, the gene that encodes the cell-cell 
adhesion protein E-cadherin, results in a heritable form of diffuse-type gastric cancer that may aid 
our understanding of sporadic disease.[36] Even though disruption of cell-cell adhesion is cited as 
an initiating event in this histologic subtype, true drivers of tumor invasion and peritoneal 
metastasis have not been characterized.[37, 38] Better understanding of molecular alterations 
associated with unique patterns of metastasis may uncover key drivers of distinct malignant 
phenotypes.[39] 
Translational and basic science research efforts have been established in our branch to investigate 
drivers of peritoneal metastasis in gastric adenocarcinoma. Clinical protocols incorporating both 
sporadic and hereditary diffuse gastric cancers (HDGC) are being conducted in parallel to 
strengthen the search for key drivers of peritoneal metastasis. Patients who undergo risk-reducing 
total gastrectomy for HDGC and those enrolled on the gastrectomy and HIPEC trial are providing 
a unique opportunity for in-depth analysis of molecular changes associated with gastric cancer 
initiation, invasion and metastasis. 
The current protocol is designed to address the challenges outlined above by evaluating a strategy 
for treating gastric cancers with peritoneal metastasis. Our aim is to investigate the use of 
intraperitoneal paclitaxel chemotherapy as an adjunct to systemic therapy for gastric cancer with 
peritoneal carcinomatosis. We hypothesize that the combination of systemic and regional therapy 
will result in disease control and improved intraperitoneal progression free survival. If so, this 
strategy could serve as a platform for adding novel anti-cancer agents for the treatment of this 
deadly disease.
1.2.4
Simulated Metastasis Assay with Relevant Tissue (SMART) Chamber 
In the Surgical Oncology Program laboratory of Dr. Jonathan Hernandez, a novel tumor modeling 
system is being developed, referred to as the Simulated Metastasis Assay with Relevant Tissue 
(SMART) Chamber. Correlative studies in proteogenomic characterization of primary and 
metastatic cancers and ex vivo tumor tissue modeling of peritoneal metastasis will be added to this 
study, utilizing the SMART Chamber.  In conjunction with ongoing laboratory work, segments of 
the peritoneum are removed from patients with peritoneal carcinomatosis at the time of operation. 
This peritoneal tissue is utilized in the SMART Chamber system to imitate conditions of metastasis 
within the abdominal cavity. This ex vivo tissue model system allows for observation of peritoneal 
metastasis, real-time cellular imaging, and manipulation of tumor-environment interactions. 
1.2.5
The SMART System
The SMART System is an important step toward our goal of realizing personalized translational 
cancer care. The ability to recapitulate the complexities of solid human tumors for the purposes of 


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11
drug development and testing has been, and remains, a major obstacle in the progress of cancer 
therapy. Despite great efforts expended on pre-clinical optimization using existing validation 
models, most drugs simply fail to demonstrate efficacy when subjected to Phase III clinical trial 
scrutiny. Our interpretation is that the currently available model systems lack the appropriate 
clinical predictive power. The reasons for the inadequacies of these model systems, which are 
largely based upon cell lines, mouse models or patient-derived xenografts, are myriad but are 
almost certainly related to the absence of the human stromal component and its intricate 
relationship with tumor cells. 
There has been a sizable expansion of oncologic pharmaceuticals that have targeted and/or 
immunomodulatory effects. However, the predictive accuracy of drug testing is predicated on 
models that accurately represent the architectural/cellular organization of the tumor and faithfully 
reflect the in vivo biology. We have satisfied many of the requirements of an ideal tumor model 
utilizing resected mesothelial metastases to create the SMART (Sample Microenvironment of 
Resected Metastatic Tumor) System. Multiple solid tumors commonly manifest with metastatic 
disease to the mesothelial surface (peritoneum, pleura, liver capsule) and some are candidates for 
metastasectomy. During these operations, resected tumor-bearing mesothelial tissue is affixed to 
a specialized platform and perfused in a sterile, oxygenated circuit at 370C to maintain normal 
physiologic parameters (Figure 1). Circulating oxygenated perfusate within the system is 
comprised of human plasma (from the patient), DMEM media, antibiotics, insulin (slow infusion). 
Figure 1: The SMART System Consisting of SMART Platform.
The SMART platform (Top Left) is designed to mount the human mesothelial tissue containing 
tumor and be suspended in the reservoir of perfusate (Bottom Left), the SMART chamber. The 
chambers suspend maximum of 4 SMART platforms and placed on stir plate in the incubator 
(Middle). The SMART system boasts a physiologic oxygenated perfusion circuit that is suitable to 


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12
keep tissue viable for up to four days. The Right Panel demonstrates the customized holder for each 
SMART platform that is imaged using complex imaging techniques. 
We have evaluated gastric adenocarcinoma, pancreatic adenocarcinoma, gastrointestinal stromal 
tumor, and breast adenocarcinoma in the SMART system and documented ex-vivo viability at 4 
days with expected immune cell populations, intact architecture, and expected mitotic activity 
(Figure 2A). RNA sequencing was performed as well to compare transcriptomics between Day 0 
and Day 4. Genes associated with hypoxia, oncogenes/tumor suppressor, cancer stem cells, 
metabolism, and epithelial-mesenchymal transition were isolated from the sequencing data and 
demonstrated conservation of transcriptomics (Figure 2B). These results ultimately demonstrate 
that tumor nodules in their native, functional microenvironment can be preserved ex vivo for 4 
days with fidelity.
 
Figure 2: Ex Vivo Normal and Tumor Preservation in the SMART System.
A (Left): Demonstration of various histologies on H&E, CD3, CD68 and Ki67 stains on Day 0 and 
Day 4. 
B (Right): Conservation of transcriptomics in hypoxic panel, oncogene/tumor suppressor, cancer 
stem cell, metabolism and EMT panels over breast, gastric, pancreatic and mesothelioma histology.
Due to the translucent nature of the mesothelial tissue, the system is readily amenable to dynamic 
interrogation with confocal, two photon and light sheet microscopy. This avenue of investigation 
is supported by a research collaborative agreement (RCA) with BioLegend and our affiliation with 
CAT-I to develop fluorescently labelled Fab fragment for live cell labelling. For example, with the 
increasing use of checkpoint inhibitors like Pembrolizumab in solid tumors, we decided to evaluate 
the drug in the SMART system using tumor from a patient with gastric adenocarcinoma and a 
patient with colorectal adenocarcinoma. We demonstrated immune cell engagement with tumors 
cells for both gastric and colorectal adenocarcinoma, and captured tumor cell lysis with the latter 


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13
(Figure 3). Such responses at the cellular level are key to understanding why some cells respond 
to the immune system while others are ostensibly resistant.
Figure 3: SMART Platforms are Valuable Tools for Drug Evaluations Such as Pembrolizumab.
Left: SMART platforms with peritoneum from a patient with gastric cancer incubated with immune 
checkpoint inhibitor Pembrolizumab for 2 days followed by Alexa488CD44/ Alexa594CD45 
antibodies. Maximum projections of 2-photon images illustrate the intimate contact between CD45-
positive cells and the cancer cells. 
Right: Timeseries montage taken from liver capsule tissue mounted on SMART platforms from a 
colorectal cancer patient with liver metastases incubated with 5 g/mL pembrolizumab for 4 hours. 
CD45-positive cells bound to CD44-positive cancer cell undergoing apoptosis.
1.2.6
Rationale for Intraperitoneal Paclitaxel Dose Increase
The primary objective of this study (19C0129) is to determine the progression free survival (PFS) 
in patients with peritoneal metastases from gastric cancer after repeated intraperitoneal (IP) 
infusion and systemic paclitaxel administration with concomitant capecitabine therapy. The first 
patient treated on study was on 07/14/2020. Since that time 4 patients have received IP and IV 
paclitaxel on study. Based on an IP paclitaxel dose of 20 mg/m2, the average dose administered to 
our patients is 34.5 mg (range 31-38.4 mg). We selected this IP paclitaxel dose based on existing 
clinical trial data in patients with gastric cancer suggesting both safety and potential efficacy for 
treating carcinomatosis. We have observed no treatment-related deaths and no toxicity attributed 
directly to the IP paclitaxel dosing. Of the 4 patients, as of 03/09/2021, three patients are now off-
treatment and one is currently undergoing a second course of therapy without any serious adverse 
events.
Objective responses have been mixed with 2 patients exhibiting stable disease after 2 courses of 
treatment; 1 patient experienced rapid progression of disease during the first course of treatment; 
and 1 patient has stable disease after 1 course of treatment. One of the patients with stable disease 
after 2 courses of treatment was subsequently enrolled and successfully treated on our Phase II 
study of gastrectomy and hyperthermic intraperitoneal chemotherapy (17C0070). 
Because an IP paclitaxel dose of 20 mg/m2 appears both safe and tolerable in our current study we 
wish to increase the IP dose of paclitaxel to 60 mg/m2 (see Section 3.2.2). The aim of this dose 
modification is to increase the likelihood of objective intraperitoneal tumor response to therapy. 


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14
The data supporting the use of 60 mg/m2 dosing of IP paclitaxel comes from both the gastric cancer 
and ovarian cancer literature. The seminal study by Armstrong et al.  [18] utilized both IP cisplatin 
(100 mg/m2) and paclitaxel (60 mg/m2) added to intravenous paclitaxel for treatment of patients 
with stage III ovarian carcinoma. Notably, the most common reason for discontinuation of IP 
chemotherapy was catheter-related complications. Although direct comparison of that study to 
19C0129 cannot be made, the fact that 60 mg/m2 of IP paclitaxel combined with IP cisplatin was 
safe, tolerable, and effective in the context of concomitant intravenous paclitaxel suggests that an 
IP paclitaxel dose of 60 mg/m2 would be safe and tolerable in our gastric cancer patients, also.
One could argue whether we should use an even higher dose of IP paclitaxel to achieve greater 
objective tumor response in our study. To that point, early studies in ovarian cancer showed a 
maximum tolerated dose (MTD) for IP paclitaxel given every 4 weeks was 150 mg/m2 [40].  That 
dose level has been associated with chemical peritonitis [41]. However, subsequent studies in 
ovarian cancer patients using 75 mg/m2 showed safety and minimal toxicity, which was most often 
attributed to abdominal discomfort and nausea [42]. Similarly, a study by Imano et al. [28] in 
patients with advanced gastric cancer used an 80 mg/m2 dose of IP paclitaxel that was well-
tolerated when combined with intravenous paclitaxel and oral S-1.


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15
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Patients must have histologically or cytologically confirmed gastric adenocarcinoma, 
including Siewert III gastroesophageal junction adenocarcinoma, confirmed by the NCI 
Laboratory of Pathology, and have provided a block or unstained slides of primary or 
metastatic tumor tissue or newly obtained fresh biopsy of a tumor lesion in case archival 
tissue sample is not available. 
2.1.1.2
Patients may be treatment naïve or have received systemic chemotherapy prior to 
enrollment: 

Trastuzumab allowed as prior treatment for HER2/neu over-expressing cancers 
as clinically indicated. 

Last dose of chemotherapy at least 2 weeks prior to enrollment with recovery to 
Grade 1 from chemotherapy-related toxicities. 
2.1.1.3
Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence of 
peritoneal carcinomatosis found at staging laparoscopy. 
2.1.1.4
Age ≥18 years. Children under the age of 18 will not participate in this study as gastric 
cancer is rare in this population.  
2.1.1.5
ECOG performance status ≤ 1 (Appendix A).
2.1.1.6
Patients must have normal organ and marrow function as defined below: 
hemoglobin
≥ 8.0 g/dL
absolute neutrophil count
≥ 1,000/mcL
platelets
≥ 100,000/mcL
total bilirubin
≤ 1.5 X institutional upper limit of normal 
AST(SGOT)/ALT(SGPT)
≤ 2.5 X institutional upper limit of normal
creatinine
< 1.5 mg/dl
OR
creatinine clearance
≥ 60 mL/min/1.73 m2 for patients with 
creatinine levels above institutional normal.
2.1.1.7
Physiologically able to undergo laparoscopy and systemic chemotherapy.
2.1.1.8
Ability of subject to understand and the willingness to sign a written informed consent 
document. 
2.1.1.9
Previous exploratory laparotomy or laparoscopy with tissue biopsy or peritoneal lavage 
is permitted.
2.1.1.10 Women of child-bearing potential and men must agree to use adequate contraception 
(hormonal or barrier method of birth control; abstinence) prior to study entry and for the 
duration of study treatment.  Should a woman become pregnant or suspect she is pregnant 


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16
while she or her partner is participating in this study, she should inform her treating 
physician immediately.
2.1.1.11 Patients must be co-enrolled in protocol 13C0176 (NCT01915225) and 17C0044 
(NCT03027427) for sample collection.
2.1.1.12 HIV-positive patients may be considered for this study only after consultation with a 
NIAID physician.
2.1.2
Exclusion Criteria
2.1.2.1
Patients who are receiving any other investigational agents.
2.1.2.2
Previous cytoreductive surgery or intraperitoneal chemotherapy.
2.1.2.3
Disseminated extra-peritoneal or solid organ metastases:

Excludes greater omentum and ovarian metastases.

Radiographic signs or clinical symptoms consistent with malignant bowel 
obstruction.
2.1.2.4
History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to Paclitaxel or Capecitabine or other agents used in study.
2.1.2.5
Previous treatment with paclitaxel or nab-paclitaxel resulting in progression of disease.
2.1.2.6
Existing peripheral neuropathy, Grade 3 or greater.
2.1.2.7
Past medical history of dihydropyrimidine dehydrogenase deficiency. 
2.1.2.8
Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with study 
requirements.
2.1.2.9
Pregnant women are excluded because paclitaxel and capecitabine can cause fetal harm 
when administered to pregnant women. Because there is an unknown but potential risk 
for adverse events in nursing infants secondary to treatment of the mother with paclitaxel 
and capecitabine, breastfeeding should be discontinued if the mother is treated with 
paclitaxel and capecitabine.
2.1.3
Recruitment Strategies
Both men and women from all races and ethnic groups are eligible for this trial. 
This protocol may be abstracted into a plain language announcement posted on NIH websites and 
on NIH social media platforms. Participants will be recruited from the current patient population 
as well as referrals at NIH.
2.2
SCREENING EVALUATION 
2.2.1
Screening Activities Performed Prior to Obtaining Informed Consent
Minimal risk activities that may be performed before the subject has signed a consent include the 
following: 

Communications with prospective subjects, via email or phone conversations


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
Review of existing medical records to include H&P, laboratory studies, etc  

Review of existing MRI, x-ray, or CT images

Review of existing photographs or videos

Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes
2.2.2
Screening Activities Performed After a Consent for Screening Has Been Signed
The following screening activities will be performed only after the subject has signed the study 
consent OR the consent for study 17C0044 (provided the procedure is permitted on that study) on 
which screening activities may also be performed. Assessments performed at outside facilities or 
on another NIH protocol within the timeframes below may also be used to determine eligibility 
per PI discretion, once a patient has signed the consent.
Unless otherwise indicated evaluations may be performed at any time prior to enrollment.

Cytologic or Histopathologic Confirmation of the Disease (at Any Time Point Prior to 
Initiation of Study Therapy) 
A block or unstained slides of primary or metastatic tumor tissue will be required from 
each participant to confirm diagnosis with analysis being performed by the Laboratory 
of Pathology, NIH. In cases where archival tissue sample is not available, a fresh biopsy 
will be done. 

History and Physical Evaluation   
o
Complete history and physical examination (including vital signs, height and 
weight as well as ECOG assessment, EKG and review of systemic treatment 
records).
o
Dietary assessment by a Registered Dietitian.
o
Concurrent medication reconciliation.
o
Consultation with NIAID physician in HIV positive subjects.

Laboratory Evaluation, within 8 weeks prior to initiation of study therapy
o
General Labs: 

CBC with differential

Acute care panel: Sodium (Na), Potassium (K), Chloride (Cl), total CO2 
(bicarbonate), Creatinine, Glucose, Urea nitrogen (BUN)  

Mineral panel: Calcium total, Magnesium total (Mg), Inorganic 
Phosphorus, Albumin 

Hepatic panel: Alkaline Phosphatase, ALT/GPT, AST/GOT, Total 
Bilirubin, Direct Bilirubin

Total Protein, total CK

PT/PTT & INR
o
HIV test, Hepatitis B surface antigen and Hepatitis C antibody.
o
Nutrition Labs: C-reactive protein, Hg A1c, Ferritin, Prealbumin, Thiamine, Iron 
and transferrin panel, Vitamin B12, Methylmalonic acid, Zinc, 25-hydroxy 
Vitamin D, folate, lipid panel (Cholesterol (total), LDL, HDL and Triglycerides). 


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18
o
Urinalysis.
o
Tumor markers: CEA, CA 19-9, CA 15-3, CA 125, CA 27-29. 
o
β- HCG test (serum) for women of child-bearing potential (within 3 days from 
study enrollment).

CT Scan with or without PET (with or without standard oral/IV contrast), within 4 weeks 
prior to initiation of study therapy
2.3
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g. when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2: CCR Participant 
Registration 
& 
Status 
Updates 
found 
at: 
https://ccrod.cancer.gov/confluence/pages/viewpage.action?pageId=73203825. 
2.3.1
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE).
2.3.2
Treatment Assignment Procedures
Cohorts
Number
Name
Description
1
Cohort A
Patients with confirmed diagnosis of gastric 
adenocarcinoma or gastroesophageal junction (Siewert 
I-III) adenocarcinoma who have received prior systemic 
chemotherapy.
2
Cohort B
Patients with confirmed diagnosis of gastric 
adenocarcinoma or gastroesophageal junction (Siewert 
I-III) adenocarcinoma who are treatment naïve.
Arms
Number
Name
Description
1
Arm 1
IP and IV paclitaxel administration with concomitant 
oral capecitabine.
Arm Assignment


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19
Patients in Cohort A and B will be directly assigned to Arm 1. 
2.4
BASELINE EVALUATION 
Tests done at screening do not need to be repeated on baseline (C1D1) if performed within 4 weeks 
prior to initiation of study therapy except:

Physical exam (including vital signs and ECOG assessment)

Laboratory Evaluations
o
CBC with differential
o
Chem 20 equivalent 
o
Serum pregnancy test (repeat if > 3 days) for women of child-bearing potential. 
Please refer to Section 2.2 for screening evaluation details.
Patients will also undergo: 

Initial laparoscopy.

CT Scan with or without PET (with or without standard oral/IV contrast)

Evaluation of extent of peritoneal carcinomatosis by method of peritoneal cancer index 
(PCI).

Placement of peritoneal chemo-infusion port.

Endoscopy with biopsy (esophagogastroduodenoscopy, EGD) if indicated.

Research Correlatives: 
o
Blood, peritoneal ascites (or peritoneal washing) and tissue sample collection as 
indicated in Section 5.
o
QOL Questionnaire (see Section 3.6.6).
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
This is a Phase II trial designed to determine the efficacy of intraperitoneal paclitaxel in 
combination with intravenous paclitaxel and oral capecitabine in patients with gastric cancer and 
intraperitoneal metastasis.  
After placing the peritoneal chemo infusion port Days 1 to 3, as dictated by clinical status, patients 
will begin intraperitoneal paclitaxel and intravenous paclitaxel (Day 1) followed by oral 
capecitabine on the evening of Day 1 to the morning of Day 15, followed by a 7-day treatment 
free interval, in each 3-week cycle.  One course will comprise 3 treatment cycles (3 weeks each; 
total 9 weeks). There will be a total of two courses for patients with an objective response or stable 
disease.
Treatment evaluation will take place after 3 cycles of treatment are completed (+/- 7 days) with 
repeat staging studies and laparoscopy to assess for treatment response. Patients with progressive 
disease will be taken off study treatment and will be followed for survival. Patients with an 
objective response or stable disease will continue to a second course of treatment. After a second 
course of treatment (+\- 7 days), patients will have repeat staging studies and laparoscopy to assess 
for treatment response. Patients with objective response will receive no further study-related 
treatment after the second course but will remain on study for determination of secondary 
endpoints. 


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In cases when a patient has an exceptional response to this treatment strategy, two treatment 
options will be discussed in a multi-disciplinary gastrointestinal malignancy meeting and discussed 
with the patient. First, continued treatment with IP and IV paclitaxel with oral capecitabine may 
be considered. The rationale is that the intervention is potentially effective and that stopping the 
therapy may not be desirable. These patients who choose continued treatment will not be evaluated 
for primary endpoint analysis.
Second, and in the setting of exceptional response with residual peritoneal disease (PCI < 10), 
cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may be considered an 
alternate treatment option. This surgery would be done off protocol under a generic standard of 
care protocol within CCR. Patients would stay on this study to be followed for survival. 
Lastly, patients may elect to stop therapy per protocol and initiate observation without active 
treatment.
The IP port and catheter will be removed at the time of study completion, or earlier if needed (such 
as surgical extraction due to port complications or patient withdrawal from the study) except in 
circumstances of death, lost to follow-up, and in cases in which patients may not be able to return 
to NIH if they progress on study (and consequently the port and catheter may remain in place). 
 


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21
3.1.1
Chemotherapy Schema 
Study Course
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
AM PM
AM PM
AM PM
AM PM
AM PM
AM PM
AM PM
Week 1
*
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 2
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 3
✓
Week 4
*
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 5
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 6
✓
Week 7
*
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 8
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Week 9
✓
× (Within Day 1 to Day 7)
IP/IV Paclitaxel *
PO Capecitabine ✓
Treatment Evaluation ×
3.2
DRUG ADMINISTRATION
3.2.1
Intraperitoneal Paclitaxel
Intraperitoneal chemotherapy will be delivered via an implantable subcutaneous-peritoneal port.  
Body surface area will be calculated at each cycle for each patient.
Patients who are concurrently receiving or requiring any of the agents listed below, which may 
increase the risk for paclitaxel/capecitabine related toxicities, will have all medications reconciled 
by a NIH Clinical Center clinical pharmacist.
The following drugs will be discontinued one week prior to administration of paclitaxel:

Nonsteroidal anti-inflammatory medications 

Aspirin 

Conivaptan 

Cyclosporine

Disulfiram 

Eliglustat

Epirubicin 

Febuxostat

Idelaslisib 

Mitotane 

Nilotinib 

Penicillamine 

Tolvaptan 


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22

Vemurafenib 

Clozapine

Echinacea 
The following drugs may be held, or doses modified, during therapy as indicated by the clinical 
pharmacist:

Metronidazole 

Gemfibrozil

Filgrastim G-CSF

Platelet inhibitors
3.2.2
Intraperitoneal and Intravenous Paclitaxel Administration
Intraperitoneal paclitaxel (60 mg/m2) will be diluted in 500 mL of 0.9% NS and warmed to 37⁰C. 
The solution will then be infused as rapidly as tolerated once per 3-week cycle on Day 1. The 
patient will then be instructed to adjust position every 15 minutes for 2 hours. 
Intravenous paclitaxel (80 mg/m2) will be administered concomitantly over 3 hours (+ 1 hour)* 
diluted in 100 to 250 mL of 0.9% NS once per 3-week cycle on Day 1.  Standard intravenous 
hypersensitivity prophylaxis (dexamethasone 20 mg, diphenhydramine 50 mg and ranitidine 50 
mg) will be given at least 30 minutes prior to intravenous paclitaxel. *Note: Refer to Section 3.3.1 
for dose delays/dose modification guidelines in the event of an adverse event.
IP and IV paclitaxel will be given at the same time. We will ask the Pharmacy to add a brightly 
colored label that says “NOT for IV use” to the IP chemo bag so that Paclitaxel IP and IV doses 
do not get reversed.
3.2.3
Capecitabine Administration 
Patients will receive a 14-day supply of oral capecitabine (825 mg/m2) to be taken twice a day 
starting the evening of Day 1 of each cycle.  Capecitabine will continue for 28 doses until the 
morning of Day 15, followed by a 7-day rest period during each 3-week cycle. Capecitabine tablets 
should be swallowed whole with water within 30 minutes after a meal.
3.2.3.1 CCR Self – Administered Study Drugs Policy Regarding Capecitabine 
All oral self-administered investigational agents will be properly accounted for, handled, and 
disposed in accordance with existing federal regulations and principles of Good Clinical Practice. 
All oral study drugs will be recorded in the patient diary found in Appendix C. This will be used 
as a memory aide for subjects. The clinical research team will maintain the primary source record. 
Subjects should be asked to bring the diary as well as unused study agent and empty containers 
with them to each study visit. If a subject goes off study while at home, the research nurse will 
ensure and document the return of the unused oral investigational agents from the participant. 
Unused investigational study agents will be disposed and destroyed per CC Pharmacy SOPs.
3.3
DOSE MODIFICATIONS
Toxicity will be evaluated before each treatment cycle according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.


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3.3.1
General Guidance for Dose Modification
To Begin the Next Treatment Cycle

Patients must have platelet count > 100,000/mcL, absolute neutrophil count > 
1,000/mcL

Non-hematologic toxicity covered to < Grade 2 (or tolerable Grade 2 or baseline)
In the event of an adverse event at least possibly related to the investigational agent, the dose of 
the investigational agent should be adjusted according to the guidelines shown in the dose 
delays/dose modifications tables shown below (Table 2 and Table 3). If an adverse event is not 
recovered in such tables, doses may be held at the discretion of the investigator for the subject’s 
safety.
Table 2: 
Table 3:
NCI-CTCE Grade 
Treatment Modification 
Grade 1 - Mild 
Mild transient reaction; infusion 
interruption not indicated: intervention not 
indicated
Treatment continued at the same 
dose. 


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Grade 2 - Moderate 
First occurrence: Treatment delay 
until toxicity has resolved to < 
Grade 2.
Second occurrence: Treatment 
delay until toxicity has resolved to 
< Grade 2; dose reduction of all 
agents by 25%.
Third occurrence: Treatment delay 
until toxicity has resolved to < 
Grade 2; dose reduction of all 
agents by 50%.
Therapy or infusion interruption 
indicated but responds promptly to 
symptomatic treatment
Fourth occurrence: Treatment 
discontinued. 
Grade 3 or Grade 4 - Severe or life 
threatening
First occurrence: Treatment delay 
until toxicity has resolved to 
< Grade 2; dose reduction of all 
agents by 25%. 
Second occurrence: Treatment 
delay until toxicity has resolved to < 
Grade 2; dose reduction of all 
agents by 50%. 
Grade 3: Prolonged; recurrence of 
symptoms following initial 
improvement. hospitalization 
indicated for clinical sequelae 
Third occurrence: Treatment 
discontinued. 
Grade 4: Life-threatening consequences; 
urgent intervention indicated
Treatment discontinued. 
 
Note: Subjects will be removed from the study treatment if they fail to recover to CTCAE Grade 
0-1, tolerable Grade 2 (or within 1 grade of starting values for pre-existing laboratory 
abnormalities), or baseline from a treatment-related adverse event within 42 days.
3.3.2
Treatment Delays and Modification for Administrative Needs
Brief interruptions and delays may occasionally be required due to travel delays, airport closure, 
inclement weather, family responsibilities, security alerts, and government holidays, etc. Delays 
of up to 1 week will not be considered protocol deviations and will not be separately reported. A 
patient that interrupts therapy for more than 3 weeks will be taken off treatment.


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3.3.3
Treatment Delays and Modifications for Medical Needs
Patients experiencing complications of their disease or other medical illness not attributable to 
disease progression, or protocol therapy may also require brief interruptions and delays that will 
not be considered protocol deviations and will not be separately reported. A patient that interrupts 
therapy for more than 3 weeks will be taken off treatment.
3.4
SUBCUTANEOUS INFUSION PORT COMPLICATIONS
Patients experiencing complications associated with or related to implanted infusion port 
including, but not limited to: malfunction, non-function, erosion, infection, leak, or severe pain 
may require medical treatment (antibiotics, pain medications, etc.) and/or surgical extraction. 
Surgical re-implantation of a port may be delayed until the cause of removal has been fully 
addressed. Delays due to port problems may require brief interruptions in treatment. Delays that 
last ≥ 5 days will be reported as Protocol Deviations. A patient that interrupts therapy for more 
than 4 weeks (30 days) will be taken off study treatment.


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3.5
STUDY CALENDAR
Treatment10    
(Course 1)
Cycle 1
(Weeks 
1-3)
Cycle 2
(Weeks 
4-6)
Cycle 3
(Weeks 
7-9)
Procedure
Screening
Baseline1
1
2
3
4
5
6
7
8
99
End 
Course 
110
Safety Visit
(30 Days 
After 
Last Study 
Intervention)
Post-
Discharge 
Visits/
Follow-
Up
(Every 3 
Months)4
Semi-
Annual 
Follow- 
Up
(Semi-
Annually 
for Years 
3-5) 4
Long-Term 
Follow-Up
(Semi-
Annually 
or 
Annually 
after Year 
5)4
Confirmation 
of Pathology
X
Relevant 
History and 
Physical 
Exam 
X
X
X
X
X
X
Height
X
ECOG 
Performance 
Status
X
X
X
X
X
X
X
Vital Signs 
and Weight
X
X
X
Laboratory Tests
Labs (as listed 
in Section 2.2 
and 2.4)
X
X
X
X
X
X
HepB, HepC 
Testing
X
Pregnancy 
Test (Serum)
X
EKG
X
Treatment
Paclitaxel (IP 
and IV)6
X
X
X
Capecitabine 
(PO)7
X
X
X
X
X
X




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2
CT and PET may be combined or substituted for one another during post-op discharge visits/follow-up (see Section 3.6.5).
3
If clinically indicated.
4
Post-Discharge/Follow-Up for patients with an objective response or stable disease will return to the NIH for follow up as indicated in Section 3.6.5.1; 
patients with no objective response will be followed for survival as indicated in Section 3.6.5.2. 
5
As indicated in Section 9.3, all subjects will be offered the opportunity to complete an NIH advanced directive form. This should be done preferably at 
baseline but can be done at any time during the study as long as the subject’s capacity to do so is retained. The completion of the form is strongly 
recommended but is not required.
6
Please refer to Section 3.2.2 for details.
7
Please refer to Section 3.2.3 for details.
8
Mandatory Biopsy will be done at baseline, at end of treatment Course 1, and end of treatment Course 2 (if given in case of stable disease or objective 
response). Leftover biopsy tissue may be used for research purposes (refer to Section 5); peritoneal ascites or peritoneal washings may be collected during 
the procedure for research into circulating tumor cell and immune subsets analyses (5.2.1). 
9
Patients will be re-evaluated for response after the first course of treatment at the 9th week, and after the second course if both courses given (refer to Section 
6.3).
10
There will be a total of two courses of treatment for patients with an objective response or stable disease. Note: If given, Course 2 will continue treatment 
and assessment as indicated for Course 1; CT/PET and laparoscopy will be performed after the completion of each course treatment for evaluation of 
response. 
11
Research blood to be collected within 7 days prior to laparoscopic staging at baseline and as indicated Section 5.


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3.6
SURGICAL GUIDELINES 
3.6.1
Preoperative Patient Management
Patients will receive standard preoperative care as appropriate to the planned surgical intervention 
and the patient’s underlying health status. This will include:

Hibiclens shower the night before operation.

Preoperative IV antibiotic administered within 2 hours prior to the start of the 
operation.  

Sequential compression devices will be placed on the lower extremities prior to the 
induction of general anesthesia. 

Subcutaneous heparin administration for venous thromboembolism prophylaxis 
prior to the induction of general anesthesia.
3.6.2
Patient Management in the Operating Room
3.6.2.1 Staging Laparoscopy and Port Placement

Staging laparoscopy will be performed to calculate PCI (Appendix B).

Intraperitoneal ports will be placed over the abdominal wall fascia on the side most 
convenient to the patient.

Prior to skin closure the port will be flushed with 10 mL of heparinized saline (100 
USP/mL) to ensure patency.
3.6.2.2 Re-Staging Laparoscopy 

After first course of treatment patients will undergo re-staging laparoscopy.

PCI will be calculated, and representative biopsies will be taken to assess response. 
3.6.3
Postoperative Care Staging Laparoscopy and Port Placement 
3.6.3.1 Patient Monitoring Staging Laparoscopy and Port Placement 
Patients will receive standard post-operative care as appropriate to the planned surgical 
intervention and the patient’s underlying health status. 
3.6.4
Discharge 
Patients will be discharged (as clinically indicated) according to standard discharge criteria.

Total hospitalization may be approximately 3-4 days.

Patients may first be eligible for discharge the day following IP paclitaxel 
administration to ensure tolerance of both chemotherapeutics. 

Patients may require evaluation by their referring physician following discharge; 
any clinically indicated laboratory testing obtained locally will be faxed to the 
Research Nurse.
3.6.5
Post-Discharge/Follow-Up 
3.6.5.1 Patients with Objective Response or Stable Disease
Patients with an objective response or stable disease will return to the NIH at 1, 3, 6, 9, 12, 15, 18, 
21 and 24 months from the date of completion of treatment. After 24 months, the patients will 
return every 6 months for Years 3-5, and every 6 months thereafter. Follow up visits may vary +/- 


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2 weeks for the first 2 years, and +/- 4 weeks thereafter. Follow up visits at NIH will include scans 
for radiological assessment and patient completion of the QOL questionnaire (only first 5 years). 
If patients are not able to come to NIH after 5 years, they will be followed by phone, videocall or 
other NIH approved remote platform contact (used in compliance with policy, including HRPP 
Policy 303) every 6 months for survival, performance status, new cancer treatment.
Patients with an objective response or stable disease who are unable to come to NIH for follow up 
visits within the first 5 years may have the option of having follow up done with a local physician 
at the recommended interval, per discretion of the PI. The healthcare team will follow up by phone 
or secure videocall/other NIH approved remote platform (used in compliance with policy, 
including HRPP Policy 303), to include at least a verbal report from the patient regarding disease 
status. Medical records from visits done with the home physician may be faxed or securely sent to 
the study team per CC policy and procedures. Evaluation may include radiological assessment for 
potential correlative studies (as indicated in Section 3.5). Patients may also complete the research 
questionnaire electronically or by phone/videocall as applicable.
Note: There will be no requirement for follow up visits, tests or procedures for patients with 
objective response or stable disease who have come off-treatment (e.g., they have elected for a 
different line of therapy elsewhere, etc.) and decide not to return to NIH or have local physician 
follow up visits (as indicated above) before 5 years from the date of completion of treatment. These 
patients will be followed from receipt of patient decision not to return to NIH or have local 
physician follow up visits onward by phone, videocall or other NIH approved remote platform 
contact (used in compliance with policy, including HRPP Policy 303) for survival, performance 
status, and new cancer treatment every 6 months for 5 years or until patient death, whichever 
comes first.
Additionally, clinically indicated imaging studies and laboratory assessments may be performed 
locally; symptom assessments may be performed remotely by phone/videocall.
3.6.5.2 Patients with No Objective Response
Patients with no objective response will be taken off study treatment and will be followed for 
survival over the phone, videocall or other NIH approved remote platform (used in compliance 
with policy, including HRPP Policy 303) annually.
3.6.6
Measurement of Health Related Quality of Life for Research
For patients fluent in English, Quality of Life questionnaires (QOL) will be completed at the pre-
treatment evaluation prior to intervention, at the end of each course, and at each post-treatment 
clinical visit (every 3 months +/- 2 weeks) for 5 years. 
Patients will be informed of the details of the QOL part of this study and reassured that their 
decision to participate will not have an effect on the application of the treatment intervention. Once 
enrolled, the patient has the right at any time to elect not to continue completing the questionnaires. 
In the event a patient goes off-study prior to completion of the follow up time points, the data 
gathered from their completed QOL questionnaires will be included in the final analysis. 
We will use tools specifically developed for assessment of QOL in gastric cancer patients: FACT-
Ga. Measures will be initially administered by an Associate Investigator Research Nurse or 
designee. The Research Nurse or designee will assess the patient’s ability to read, and if the patient 
is unable to read, it will not be administered. The Research Nurse or designee will administer the 


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questionnaires providing a firm surface at a table or clipboard and pencil. QOL data will be 
collected in stored in Labmatrix. If it becomes available, electronic versions of QOL questionnaires 
will be developed with the assistance of Jason Levine, MD, and will be offered to patients via 
secure, web-based application. The patients will be directed to complete the questionnaires using 
the following instructions:
We would like to better understand how you and other persons in this study feel, how 
well you are able to do your usual activities, and how you rate your health while you 
are participating in this research study. To help us better understand these things about 
you and other persons participating in this study, please complete these two 
questionnaires about your quality of life. Both questionnaires should not take longer 
than 15 minutes to complete.
The questionnaires are simple to fill out. Be sure to read the instructions on the top 
each questionnaire. Remember, this is not a test and there are no right or wrong 
answers. Choose the response that best represents the way you feel. I will quickly 
review the questionnaires when you are done to make sure that all the items have been 
completed. Please answer all the items with the response that is most applicable.
You should answer these questions by yourself. Your husband/wife or other family 
members or friends should NOT assist you in completing the questionnaires. Please fill 
out the questionnaires now. Return the questionnaires to me when you have completed 
them. We will be asking you to complete these again during some of your follow up 
visits.  If you have any questions, please ask.
The Research Nurse or designee will request that the patient complete the questionnaires prior 
to seeing the physician, as the interaction between the patient and physician may influence the 
patient’s answers to the questionnaires.
Once the patient has completed the questionnaires, the Research Nurse or designee, will review 
them for completeness and thank the patient for their cooperation. Subsequent measurements 
will be administered by the Associate Investigator Research Nurse, or designee, when the 
patient returns for follow-up visits as specified in Section 3.6.5.
3.7
COST AND COMPENSATION 
3.7.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center. If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not covered 
by insurance company. Medicines that are not part of the study treatment will not be provided or 
paid for by the NIH Clinical Center.    
3.7.2
Compensation
Participants will not be compensated on this study.
3.7.3
Reimbursement 
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 


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participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.
3.8
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
Prior to removal from study, effort must be made to have all subjects complete a safety visit 
approximately 30 days following the last dose of study therapy.
Note: As overall survival is a study objective, patients may be removed from treatment but remain 
on-study for long-term follow-up (Section 3.6.5). 
3.8.1
Criteria for Removal from Protocol Therapy

Completion of protocol therapy 

Progression of disease

Participant requests to be withdrawn from active therapy

Investigator discretion

Enrollment on another study (Note: Patient may remain on-study but off therapy for 
survival endpoint data, to include enrollment onto another treatment protocol.)

Positive pregnancy test

Patient does not follow protocol-related instructions given by the study team

Malfunction of IP port which cannot be salvaged   
3.8.2
Off-Study Criteria

Participant requests to be withdrawn from study

Investigator discretion

Death

PI decision to end the study

Lost to follow up

Screen failure
3.8.3
Lost to Follow-Up
A participant will be considered lost to follow-up if he or she fails to return for 4 scheduled visits 
and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:

The team will attempt to contact the participant and reschedule the missed visit within 
3 weeks and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study.

Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls 
and, if necessary, an IRB approved certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record or study file. 


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
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
4
CONCOMITANT MEDICATIONS/MEASURES
During the post-operative period, patients will receive all standard of care supportive measures, 
including possible nasogastric tube drainage and bowel rest for ileus, pulmonary toilet teaching 
and incentive spirometry to prevent atelectasis, transfusions, and antibiotics as indicated. 
5
CORRELATIVE STUDIES
5.1
BIOSPECIMEN COLLECTION TABLE
Test/Assay
Volume 
(approx.)
Tube 
Type 
or 
Medium*
Collection 
Points 
(+/-48hrs)
Location 
of 
Specimen 
Processing/
Storage
Location of 
Specimen 
Analysis
Blood,
7.5 mL
CellSave 
Preservation 
Tubes
Baseline,
Weeks 3 
and 6,  
End of 
Course
Trepel Lab 
Trepel Lab 
Circulating 
Tumor Cell and 
Immune Subset 
Analysis 
Peritoneal 
ascites,
≥ 10 mL
OR
Peritoneal 
washings,
50 mL
(For 
Either: with
50 mL of 
PBS Buffer)
Specimen 
Cup with 
Anti-
Coagulant 
(Heparin)
Baseline,
End of 
Course
Trepel Lab
Trepel Lab
Pharmacokinetic 
(PK) Studies
Blood,
6 mL 
EDTA, 
Lavender top
Pre-IV/IP 
infusion,
Post-IV/IP 
infusion at 
1, 2, 4, 8, 
Blood 
Processing Core 
(BPC)
Blood Processing 
Core (BPC)


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and 24 
hours 
Tumor 
tissue
Nunc 
cryovial
Baseline,
End of 
Course
Blood 
Processing Core 
(BPC)
Blood Processing 
Core (BPC)
Pharmacogenetic 
Studies
Blood,
3 mL
EDTA, 
Lavender top
(K2EDTA 
BD 
Biosciences 
tube 
preferred)
Baseline
Blood 
Processing Core 
(BPC)
Blood Processing 
Core (BPC)
Proteogenomic 
Analysis
Tumor 
tissue
with 
mesothelial 
metastases
Nunc 
cryovial
Baseline,
End of 
Course
Blood 
Processing Core 
(BPC)
Dr. Hernandez’s 
Lab
* Tubes/media may be adjusted at the time of collection based upon materials available if approved by 
the PI/laboratory investigator.
Blood samples for biomarker studies will be processed and stored in the Blood Processing Core 
(BPC) and sample processing will be per established techniques, unless indicated otherwise.
The amount of blood that may be drawn from adult patients for research purposes shall not exceed 
10.5 mL/kg or 550 mL, whichever is smaller, over any eight-week period.
Note: See Appendix D for a general reference of specimens and collection timepoints research 
specimens of IP and IV Paclitaxel patients to be collected, stored, tracked, analyzed for correlative 
studies and disposed of as specified in protocol 13C0176 specifically for 13C0176 correlative 
studies, noting that this information is only to be used as an overview for reference purposes; 
these noted biospecimens will be collected only as indicated on 13C0176, in which the patients 
will be co-enrolled. 
5.2
SAMPLE COLLECTION AND PROCESSING
5.2.1
Circulating Tumor Cell and Immune Subset Analysis
Blood samples and peritoneal ascites or peritoneal washings collected for circulating tumor cell 
(CTC) and immune subsets analyses will be directly transported to the laboratory of Dr. Jane 


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Trepel (Neckers), where samples will be freshly analyzed for CTC and barcoded and viably stored 
for immune subsets analysis. Circulating tumor cell and immune subset samples will be evaluated 
in order to determine the impact of the study intervention.
5.2.2
Pharmacokinetic (PK) Studies
All collected specimens for pharmacokinetic (PK) analysis will be directly transported to the Blood 
Processing Core (BPC), where samples will be processed, databased, barcoded, and stored frozen. 
Tumor tissue biopsies for will be performed at baseline, and at end of course. Portions of collected 
tumor tissue will be analyzed for pharmacokinetic (PK) at pre- and post-intervention by measuring 
the tissue concentrations of paclitaxel using validated assays in the Figg Lab’s Clinical 
Pharmacology Program. 
Blood will be collected for PK analysis at pre- and 1, 2, 4, 8, and 24 hours post-IV/IP infusion. 
Systemic plasma concentrations of paclitaxel in patient blood samples will be analyzed by Dr. 
Figg’s Lab for longitudinal studies. 
5.2.3
Pharmacogenetic Studies
All collected specimens for pharmacogenetic analysis will be directly transported to the Blood 
Processing Core (BPC), where samples will be processed, databased, barcoded, and stored frozen. 
One blood sample per patient will be collected in a purple top tube for pharmacogenetic studies to 
analyze the genomic DNA and assess genotype of the most relevant drug metabolizing enzymes 
and transporters (DMET). DNA will be analyzed for 4,627 genetic variations in 1,191 drug 
disposition genes, including cytochrome P450s (CYPs), Glutathione transferases (GSTs), 
sulfotransferases (SULTs), as well as genes involved in facilitation of drug transporters, global 
regulation of drug metabolizing/transporting proteins, drug binding proteins, and drug targets.
5.2.4
Proteogenomic Characterization of Primary and Metastatic Cancers
Peritoneal biopsy tumor tissue with resected mesothelial metastases collected during the study 
procedure will be sent to Dr. Hernandez’s Laboratory for ex vivo analysis utilizing the SMART 
(Sample Microenvironment of Resected Metastatic Tumor) System. Ex vivo tumor tissue modeling 
of peritoneal metastasis will be performed utilizing the SMART Chamber (Section 1.2.4) and 
resected mesothelial metastases will undergo ex vivo SMART System modeling (as outlined in 
Section 1.2.5) in the laboratory to support the identification of underpinnings of interventional 
chemotherapeutic and immunomodulatory agent effects. 
5.3
SAMPLE STORAGE, TRACKING AND DISPOSITION
Samples will be ordered in CRIS and tracked through the Clinical Trial Data Management system. 
Should a CRIS screen not be available, the CRIS downtime procedures will be followed. Samples 
will not be sent outside NIH without appropriate approvals and/or agreements, if required.
5.3.1
Samples Managed by Dr. Figg’s Blood Processing Core (BPC) 
5.3.1.1
BPC Contact Information 
Please e-mail 
 at least 24 hours before transporting samples (the 
Friday before is preferred).
For sample pickup, page 


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For immediate help, call 
 (main blood processing core number) or, if no answer, 
 (main clinical pharmacology lab number).
For questions regarding sample processing, contact 
5.3.1.2
Sample Data Collection
All samples sent to the Blood Processing Core (BPC) will be barcoded, with data entered and 
stored in the Labmatrix utilized by the BPC. This is a secure program, with access to Labmatrix 
limited to defined Figg lab personnel, who are issued individual user accounts. Installation of 
Labmatrix is limited to computers specified by Dr. Figg. These computers all have a password 
restricted login screen. 
Labmatrix creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to subjects without Labmatrix access. The data recorded for each sample includes the patient 
ID, name, trial name/protocol number, time drawn, cycle time point, material type, as well as box 
and freezer location. Patient demographics associated with the clinical center patient number are 
provided in the system. For each sample, there are notes associated with the processing method 
(delay in sample processing, storage conditions on the ward, etc.).
5.3.1.3
Sample Storage and Destruction
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20 or -800C according 
to stability requirements. These freezers are located onsite in the BPC and offsite at NCI Frederick 
Central Repository Services in Frederick, MD. Visitors to the laboratory are required to be 
accompanied by laboratory staff at all times. 
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in Labmatrix. All 
researchers are required to sign a form stating that the samples are only to be used for research 
purposes associated with this trial (as per the IRB approved protocol) and that any unused samples 
must be returned to the BPC. It is the responsibility of the NCI Principal Investigator to ensure that 
the samples requested are being used in a manner consistent with IRB approval. 
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting the 
rights to use the material.
If, at any time, a patient withdraws from the study and does not wish for their existing samples to 
be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed (or returned to the patient, if so requested). The PI will record any loss 
or unanticipated destruction of samples as a deviation. Reporting will be per the requirements of 
Section 7.2.
Sample bar-codes are linked to patient demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of 
Labmatrix. It is critical that the sample remains linked to patient information such as race, age, 
dates of diagnosis and death, and histological information about the tumor, in order to correlate 
genotype with these variables.
5.3.2
Laboratory of Pathology
Tissues designated for clinical diagnostics are transported to the Laboratory of Pathology (LP) 
where they are examined grossly and relevant portions are fixed, embedded in paraffin and 




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database. Only this bar code will be recorded on the sample vial and the vials will not be traceable 
back to patients without authorized access to the NCI Labmatrix database.
Samples are stored in freezers at -80°C (sera, plasma, tissue samples) or under liquid nitrogen 
(cells), according to stability requirements. These freezers are located onsite at Dr. Hernandez’s 
laboratory. Access to samples from a protocol for research purposes will be by permission of the 
Principal Investigator.
5.3.5
Protocol Completion/Sample Destruction
All specimens obtained in the protocol are used as defined in the protocol. Any specimens that are 
remaining at the completion of the protocol will be stored in the conditions described below. The 
study will remain open so long as sample or data analysis on this protocol continues. Samples from 
consenting subjects will be stored until they are no longer of scientific value or if a subject 
withdraws consent for their continued use, at which time they will be destroyed.
If the patient withdraws consent the participants data will be excluded from future distributions, 
but data that have already been distributed for approved research use will not be able to be 
retrieved.
Any specimens that are remaining at the completion of the protocol will be transferred to protocol 
13C0176 as all patients will have prospectively consented to this study. Access to these samples 
will only be granted following IRB approval of an additional protocol, granting the rights to use 
the material. The PI will record any loss or unanticipated destruction of samples as a deviation. 
Reporting will be per the requirements of Section 7.2.
5.3.6
Management of Results
Subjects will be contacted if a clinically actionable gene variant is discovered. Clinically 
actionable findings for the purpose of this study are defined as disorders appearing in the American 
College of Medical Genetics and Genomics recommendations for the return of incidental findings 
that is current at the time of primary analysis. (A list of current guidelines is maintained on the 
CCR intranet: https://ccrod.cancer.gov/confluence/display/CCRCRO/Incidental+Findings+Lists). 
Subjects will be contacted at this time with a request to provide a blood sample to be sent to a 
CLIA certified laboratory. 
If the research findings are verified in the CLIA certified lab, the subject will be offered the 
opportunity to come to NIH (at our expense) to have genetic education and counseling with the 
NCI Genetics Branch to explain this result. If the subject does not want to come to NIH, a referral 
to a local genetic healthcare provider will be provided (at their expense). 
This is the only time during the course of the study that incidental findings will be returned. No 
interrogations regarding clinically actionable findings will be made after the primary analysis. 
6
DATA COLLECTION AND EVALUATION
6.1
DATA COLLECTION
For the purposes of the research sample analyses and correlation with clinical outcomes, 
demographic information, histology, operative and peri-operative interventions, pathologic 
findings, laboratory and imaging parameters (performed as part of routine or protocol specified 
patient care) may be collected on this study. The PI will be responsible for overseeing entry of data 
into a 21 CFR Part 11-compliant data capture system provided by the NCI CCR and ensuring data 


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accuracy, consistency and timeliness. The principal investigator, associate investigators/research 
nurses and/or a contracted data manager will assist with the data management efforts. Primary and 
final analyzed data will have identifiers so that research data can be attributed to an individual 
human subject participant.
All adverse events, including clinically significant abnormal findings on laboratory evaluations, 
regardless of severity, will be followed until return to baseline or stabilization of event. 
Document AEs from the first study intervention, Study Day 1, through 30 days after the subject 
received the last product administration. After 30 days, only adverse events which are serious and 
related to the study intervention need to be recorded. 
An abnormal laboratory value will be recorded in the database as an AE only if the laboratory 
abnormality is characterized by any of the following:

Results in discontinuation from the study.

Is associated with clinical signs or symptoms. 

Requires treatment or any other therapeutic intervention.

Is associated with death or another serious adverse event, including hospitalization. 

Is judged by the Investigator to be of significant clinical impact.

If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 
End of Study Procedures: Data will be stored according to HHS, FDA regulations and NIH 
Intramural Records Retention Schedule as applicable. 
Loss or Destruction of Data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, this will be reported expeditiously per 
requirements in Section 7.2.1.
6.1.1
Routine Data Collection
Following enrollment, graded adverse events will be described in the source documents, reviewed 
by the designated research nurse, confirmed by the PI and captured in a 21 CFR Part 11-compliant 
data capture system provided by the NCI CCR. No Grade 1 adverse events will be recorded.
Laboratory events will be captured as follows:

During hospitalization for the staging laparoscopy and intraperitoneal port placement 
procedure, only the admission labs, first morning labs drawn after 4 AM, and labs that 
support the diagnosis of a reportable event will be uploaded into the study database.

In the post-operative and treatment period, including laboratory values obtained at sites 
other than the NIH Clinical Center, only the following values will be captured in the study 
database:
o
Hemoglobin, total white blood cell count, absolute neutrophil count, platelet count.
o
PT, PTT, or INR.
o
Creatinine, ALT, AST, total and direct bilirubin.
o
Any unexpected laboratory abnormality ≥ Grade 2 possibly, probably or definitely 
related to the surgical intervention.


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6.1.1.1 Exclusions to Routine Data Reporting
The following adverse events will be captured only in the source documents and will not be 
reported in the study database:
For the duration of the study:

Laboratory values that do not support the diagnosis of a reportable event.
During hospitalization for surgical port placement and staging laparoscopy:

Grade 2 events except unexpected events that are possibly, probably or definitely 
related to the research.
During the intraperitoneal and oral chemotherapy phase:

Grade 2 events except unexpected events that are possibly, probably or definitely 
related to the research.

Note: Events that result in hospitalization for convenience will not be reported.
Concomitant medications:

Only those medications that the patient is taking at baseline on a routine basis, prior 
to intraperitoneal paclitaxel (as indicated in Section 3.2.1), or medications that 
cause an AE will be captured in the study database. (Thus, one-time medications, 
PRN medications, and medications given to treat adverse events will not be 
captured in the study database.)
6.2
DATA SHARING PLANS
6.2.1
Human Data Sharing Plan
What data will be shared?
I will share human data generated in this research for future research as follows:
o
Coded, linked data in an NIH-funded or approved public repository. 
o
Coded, linked in BTRIS (automatic for activities in the Clinical Center).
o
Coded, linked or identified data with approved outside collaborators under appropriate 
agreements. 
How and where will the data be shared?
Data will be shared through: 
o
An NIH-funded or approved public repository: clinicaltrials.gov, dbGaP.
o
BTRIS (automatic for activities in the Clinical Center).
o
Approved outside collaborators under appropriate individual agreements.
o
Publication and/or public presentations.
When will the data be shared?
o
Before publication.
o
At the time of publication or shortly thereafter.


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6.2.2
Genomic Data Sharing Plan
Unlinked genomic data will be deposited in public genomic databases such as dbGaP in 
compliance with the NIH Genomic Data Sharing Policy.
6.3
RESPONSE CRITERIA
For the purposes of this study, patients will be re-evaluated for response after first course (and 
after second course if both courses given) of treatment (1 course = 9 weeks) with IP/IV Paclitaxel 
and PO capecitabine. 
Radiographically evident/measurable disease will be evaluated for response and progression in 
this study using the new international criteria proposed by the revised Response Evaluation Criteria 
in Solid Tumors (RECIST) guideline (version 1.1).[43] Changes in the largest diameter 
(unidimensional measurement) of the tumor lesions and the shortest diameter in the case of 
malignant lymph nodes are used in the RECIST criteria. The determination of response of 
subradiographic intraperitoneal disease will be evaluated using the criteria indicated in 
Section 6.3.1.
6.3.1
Disease Parameters 
Objective response will be declared in patients who meet at least one of the following criteria:

A reduction in PCI score of greater than or equal to 4 points from baseline PCI.

Histopathologic evidence of tumor treatment effect in representative peritoneal biopsies 
obtained at the end of treatment course by re-staging laparoscopy.

Resolution of small volume ascites for patients in whom ascites was previously 
documented.
Stable disease will be declared in patients who meet at least one of the following criteria:

Absence of new intra-peritoneal or extra-peritoneal disease.

A PCI score within 2 points of baseline PCI (e.g., baseline PCI +/- 2).
Intra-peritoneal (IP) progressive disease will be defined as:

Increase in PCI of score of greater than 4 points from baseline PCI.

New ascites requiring repeat (more than 1) therapeutic paracentesis
o
Ascites need not be positive for malignant cytology.

Malignant bowel obstruction.

New intraperitoneal nodules or masses concerning for peritoneal metastasis
o
If imaging studies are inconclusive, percutaneous biopsy may be used to confirm.
o
If biopsy is determined not feasible, then repeat interval imaging may be used.
o
In the case of interval imaging, if the previous inconclusive findings are confirmed 
as disease, then the original date of the inconclusive/suspicious findings will be 
used for date of progression.

Decline in performance status not attributed to other medical causes.
Extra-peritoneal (distant) progressive disease will be defined as:

New extraperitoneal and/or solid organ (i.e., liver) metastasis.


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6.3.2
Methods for Evaluation of Measurable Disease
Staging laparoscopy: The PCI scoring system along with tissue biopsy and intra-operative video 
or image recording will be used to evaluate and document measurable disease. 
Chest x-ray: Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung. However, CT is preferable.
Conventional CT and MRI: This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less. If CT scans have slice thickness greater 
than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness. MRI is 
also acceptable in certain situations (e.g. for body scans).
Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal resolution; 
however, there are many image acquisition variables involved in MRI, which greatly impact image 
quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI is variable 
globally. As with CT, if an MRI is performed, the technical specifications of the scanning 
sequences used should be optimized for the evaluation of the type and site of disease. Furthermore, 
as with CT, the modality used at follow-up should be the same as was used at baseline and the 
lesions should be measured/assessed on the same pulse sequence. It is beyond the scope of the 
RECIST guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body 
parts, and diseases. Ideally, the same type of scanner should be used, and the image acquisition 
protocol should be followed as closely as possible to prior scans. Body scans should be performed 
with breath-hold scanning techniques, if possible.
PET-CT: At present, the low dose or attenuation correction CT portion of a combined PET-CT is 
not always of optimal diagnostic CT quality for use with RECIST measurements. However, if the 
site can document that the CT performed as part of a PET-CT is of identical diagnostic quality to 
a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT can be used for 
RECIST measurements and can be used interchangeably with conventional CT in accurately 
measuring cancer lesions over time. Note, however, that the PET portion of the CT introduces 
additional data which may bias an investigator if it is not routinely or serially performed.
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of 
CT in selected instances.
Endoscopy: Such techniques may be useful to confirm progression of disease when images are 
captured and/or biopsies are obtained.
Tumor markers:  Tumor markers alone cannot be used to assess response. If markers are initially 
above the upper normal limit, they must normalize for a patient to be considered in complete 
clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and 
PSA response (in recurrent prostate cancer) have been published. In addition, the Gynecologic 
Cancer Intergroup has developed CA-125 progression criteria which are to be integrated with 
objective tumor assessment for use in first-line trials in ovarian cancer. 


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FDG-PET: While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in assessment 
of progression (particularly possible 'new' disease). New lesions on the basis of FDG-PET imaging 
can be identified according to the following algorithm:
a) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion.
b) No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDGPET 
at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the 
positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional 
follow-up CT scans are needed to determine if there is truly progression occurring at that 
site (if so, the date of PD will be the date of the initial abnormal FDG-PET scan). If the 
positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that is 
not progressing on the basis of the anatomic images, this is not PD
c) FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in 
cases where a residual radiographic abnormality is thought to represent fibrosis or scarring. 
The use of FDG-PET in this circumstance should be prospectively described in the protocol 
and supported by disease-specific medical literature for the indication. However, it must 
be acknowledged that both approaches may lead to false positive CR due to limitations of 
FDG-PET and biopsy resolution/sensitivity.
Note: A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater 
than twice that of the surrounding tissue on the attenuation corrected image.
Cytology, Histology: These techniques can be used to confirm progression or recurrence of 
disease. The cytological confirmation of the neoplastic origin of any ascites that appears or 
worsens during treatment when the measurable tumor has met criteria for response or stable 
disease is mandatory to differentiate between response or stable disease (an effusion may be a side 
effect of the treatment) and progressive disease.
6.3.3
Progression-Free Survival
Intraperitoneal PFS is defined as the duration of time from date of placement of intraperitoneal 
catheter and first dose of IP paclitaxel, to the date of first observation of progressive disease within 
the peritoneal cavity (increase in PCI from baseline or new ascites requiring repeat drainage; see 
Section 6.3.1), or death, whichever comes first. Extraperitoneal DFS (i.e., anything other than 
peritoneal surface disease progression) is defined as the duration of time from initiation of therapy 
to the date of first observation of progressive disease at sites other than the peritoneal surface, such 
as the liver, lymph nodes, and any other solid organs outside the peritoneal cavity.
6.4
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study. The descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting. 
All appropriate treatment areas should have access to a copy of the CTCAE version 5.0. A copy 
of 
the 
CTCAE 
version 
5.0 
can 
be 
downloaded 
from 
the 
CTEP 
web 
site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).


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7
NIH REPORTING REQUIREMENTS/DATA SAFETY MONITORING PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#HRPPPolicies-
800Series-ComplianceandResearchEventReportingRequirements.
7.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING/IRB REPORTING
7.2.1
Expedited Reporting
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802: Non-Compliance Human Subjects Research found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#HRPPPolicies-
800Series-ComplianceandResearchEventReportingRequirements. 
7.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#HRPPPolicies-
800Series-ComplianceandResearchEventReportingRequirements. 
7.3
NCI CLINICAL DIRECTOR REPORTING 
Problems expeditiously reported to the OHSRP in iRIS will also be reported to the NCI Clinical 
Director.  A separate submission is not necessary as reports in iRIS will be available to the Clinical 
Director.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email to the Clinical Director unless they are due to progressive 
disease.  
To report these deaths, please send an email describing the circumstances of the death to the 
Clinical Director/designee at NCICCRQA@mail.nih.gov within one business day of learning of 
the death.
7.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
7.4.1
Principal Investigator/Research Team
The clinical research team will meet regularly on a weekly basis when patients are being actively 
treated on the trial to discuss each patient. Decisions about dose level enrollment and dose 
escalation if applicable will be made based on the toxicity data from prior patients. 
All data will be collected in a timely manner and reviewed by the principal investigator. Events 
meeting requirements for expedited reporting as described in Section 7.2.1 will be submitted 
within the appropriate timelines.
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 
research staff.


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8
STATISTICAL CONSIDERATIONS
8.1
STATISTICAL HYPOTHESES
8.1.1
Primary Endpoint
Separately by cohort based on prior systemic treatment, determine the progression free survival 
(PFS) in patients with peritoneal metastases from gastric cancer after repeated intraperitoneal 
chemotherapeutic infusion and systemic paclitaxel administration with concomitant capecitabine 
therapy.
8.1.2
Secondary Endpoints

Determine intra-peritoneal PFS (iPFS).

Determine distant (extra-peritoneal) disease-free survival.

Determine the frequency of objective histopathologic response to therapy. 

Describe the morbidity of this treatment strategy.

Determine overall survival.
8.1.3
Exploratory Endpoints

Evaluate the impact of repeated intraperitoneal chemotherapeutic infusion (IPC) and 
systemic paclitaxel administration with concomitant capecitabine therapy on circulating 
tumor cells and immune subsets.     

Determine the pharmacokinetics of repeated intraperitoneal chemotherapeutic infusion 
(IPC) and systemic paclitaxel administration with concomitant capecitabine therapy in 
patients with peritoneal metastases from gastric cancer.

Evaluate the genomic DNA and genotype in patients with peritoneal metastases from 
gastric cancer in order to determine the most relevant drug metabolizing enzymes and 
transporters (DMET) through pharmacogenetic analyses.

Define the risk of developing peritoneal metastasis in gastric cancer, and other associated 
cancers, through genotype/phenotype correlations.

Determine the molecular changes and mechanisms of tumor initiation, invasion and 
metastasis in gastric cancers with peritoneal metastasis.

Evaluate chemotherapeutic and immunotherapeutic agent effects of systemic paclitaxel 
administration with concomitant capecitabine therapy in patients with peritoneal 
metastases from gastric cancer using a novel ex-vivo platform, the SMART System.
8.2
SAMPLE SIZE DETERMINATION
The goal will be to determine if the IV/IP paclitaxel and oral treatment with capecitabine described 
above could be associated with an 11-month median progression free survival (PFS) compared to 
a maximum 6 months median PFS based on historical controls. 
Patients will enroll in two cohorts: those treated with prior systemic chemo and those who are 
treatment naïve. In each of these two cohorts, with 32 evaluable patients receiving the proposed 
therapy,* assuming accrual would take place over approximately 4 years, and that there would be 
at least 12 months of additional potential follow-up after the last patient has begun the treatment 
on protocol, there would be 80% power to determine whether there is a difference between a 
median 5 month PFS beginning at the date IV/IP paclitaxel therapy starts and an improved 9 month 
PFS, with a one sided 0.10 alpha level test, using the method of Brookmeyer and Crowley.[44] In 


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practice, a Kaplan-Meier curve beginning at the initiation of treatment, and appropriate confidence 
intervals at selected time points, will be provided to help interpret results relative to the expected 
results. 
*Note: Per amendment version date 03/09/2021, the dose level of intraperitoneal paclitaxel in this 
protocol has been increased from 20 mg/m2 to 60 mg/m2, and therefore, the primary endpoint 
evaluation on this study will focus on patients treated at the higher (60 mg/m2) dose level. Subjects 
already receiving the study intervention prior to amendment approval will remain at the initial 
dosage (1.2.6); no intra-patient dose escalation will occur on this study. 
It is expected that 8-10 patients per year may be enrolled to each cohort in this protocol, a total of 
16-20 per year; thus, accrual is expected to be completed within approximately 4 years. Following 
the amendment dated 03/09/2021, in which the dose level of intraperitoneal paclitaxel was 
increased, the primary endpoint evaluation will focus on patients treated at the higher (60 mg/m2) 
dose level. With a requirement for 32+32=64 evaluable patients, to allow for the 4 subjects treated 
at the lower (20 mg/m2) dose level of intraperitoneal paclitaxel as well as a small number of 
inevaluable patients, the accrual ceiling will be set at 74 patients.
8.3
POPULATIONS FOR ANALYSES
Intention to treat: any subjects who enroll onto the trial and provide consent and who receive an 
intraperitoneal port and receive one cycle of IV/IP chemotherapy will be included in analyses.
8.4
STATISTICAL ANALYSES
8.4.1
General Approach
Determine the progression free survival (PFS) for patients treated on the protocol using a Kaplan-
Meier curve.
8.4.2
Analysis of the Primary Endpoints
In each of the cohorts, based on the patients treated at the 60 mg/m2 dose of intraperitoneal 
paclitaxel (refer to Section 8.2), a Kaplan-Meier curve will be constructed for PFS beginning at 
the date IP chemotherapy begins, and the median PFS in months will be reported along with 80% 
and 95% two-sided confidence intervals. Progression of disease in any body site will be considered 
events for this analysis.  
8.4.3
Analysis of the Secondary Endpoint
Intra-peritoneal progression free survival (iPFS) will be determined based on the identification of 
only intraperitoneal sites (e.g., new, malignant ascites, peritoneal nodules, ovarian metastases, etc.) 
of disease progression using a Kaplan-Meier analysis, using only these progression sites as events. 
The distant (extra-peritoneal) disease free survival (dDFS) will be determined based on 
identification of only distant sites of disease progression, such as lungs or intra-parenchymal liver, 
using a Kaplan-Meier analysis, using only these progression sites as events. A Kaplan-Meier curve 
will be constructed beginning at the date IP chemotherapy begins and the median iPFS and dDFS 
in months will be reported along with 80% and 95% two-sided confidence intervals. The frequency 
of objective histopathologic response to therapy will be based on patients with metastatic tumors 
that are biopsied at the end of a course of therapy and graded according to standard pathologic 
techniques.


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Overall survival will be estimated by the Kaplan-Meier method, along with the median OS and a 
95% confidence interval on the median.
The morbidity of this treatment strategy will be reported using frequencies of complications and 
adverse events as well as any descriptive material needed for clarification.
8.4.4
Safety Analyses
None, other than description of morbidity of the treatment strategy.
8.4.5
Baseline Descriptive Statistics
Baseline demographic characteristics will be reported.
8.4.6
Planned Interim Analysis
None.
8.4.7
Sub-Group Analysis
None.
8.4.8
Tabulation of Individual Participant Data
None.
8.4.9
Exploratory Analysis
Exploratory analyses on this study will aim to evaluate peritoneal cytology, tumor deposit, and 
plasma circulating tumor cell response. Peritoneal washings for cytology and peritoneal biopsies 
taken at baseline and at the end of course will provide information regarding immediate changes 
due to treatment as well as longitudinal information across treatments. Evaluating the response of 
circulating tumor cells to intraperitoneal delivery of chemotherapy will provide additional insight 
into the overall disease response. Tumor cell expression profiles and peritoneal immune cell 
profiles will be evaluated to identify potential biomarkers that are predictive of response to 
treatment.

Evaluation of circulating tumor cell (CTC) and immune subsets will be undertaken in 
order to determine the impact of the study intervention on the difference in the CTC 
levels between the time points; the Wilcoxon rank-sum test will be utilized for 
determination and testing for statistical significance. If multiple statistical tests of these 
laboratory-based parameters are performed, the results will be reported without any 
formal correction for multiple comparisons. 

Pharmacokinetic data from pre- and post-intervention analysis of blood and tumor biopsy 
tissues from study timepoints will be studied using longitudinal and paired analysis 
methods.

Analysis of patient blood for pharmacogenetic studies will be done to evaluate the 
genomic DNA and genotype of targeted drug metabolizing enzymes and transporters 
(DMET).
Ex vivo analysis of peritoneal biopsy tumor tissue with resected mesothelial metastases by Dr. 
Hernandez’s lab will be performed the SMART System to support the identification of 
underpinnings of interventional chemotherapeutic and immunomodulatory agent effects.


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9
HUMAN SUBJECTS PROTECTIONS
9.1
RATIONALE FOR SUBJECT SELECTION
Patients with a diagnosis of gastric cancer will be eligible for this study. Eligibility assessment will 
be made solely on the patient’s medical status. Recruitment of patients on this study will be through 
standard CCR mechanisms. No special recruitment efforts will be conducted. The investigational 
nature and objectives of this trial, the procedure and the treatments involved, the attendant risks 
and discomforts, potential benefits and potential alternative therapies will be carefully explained 
to the subjects in the clinic setting and in the hospital prior to treatment and prior to obtaining a 
signed informed consent. This is particularly important for this study because of the nature by 
which the treatment is given. The patients must subject themselves to a major operative procedure 
with the attendant risks and complications associated with it in order to receive treatment without 
any assurance of benefit from the treatment.
9.2
PARTICIPATION OF CHILDREN
The chemotherapeutic regimen in this study is not established in children. Both paclitaxel and 
capecitabine are not medications commonly used in the pediatric population. There is little known 
regarding the pharmacodynamics or pharmacokinetics in children. Additionally, there has been 
limited literature in which paclitaxel has been associated with central nervous toxicity and in rare 
cases death. In addition to the experimental nature of the chemotherapy combination, this protocol 
calls for repeated surgical intervention resulting in discomfort and hazards for the patients. Should 
results of this study indicate efficacy in treating gastric cancer, which is not responsive to other 
standard forms of therapy, future research can be conducted in the pediatric population to evaluate 
potential benefit in that patient population.
9.3
PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT
Adults unable to give consent are excluded from enrolling in the protocol. However, re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. For this reason and because there is a prospect of direct benefit from 
research participation (Section 9.4), all subjects will be offered the opportunity to fill in their 
wishes for research and care, and assign a substitute decision maker on the “NIH Advance 
Directive for Health Care and Medical Research Participation” form so that another person can 
make decisions about their medical care in the event that they become incapacitated or cognitively 
impaired during the course of the study. Note: The PI or AI will contact the NIH Ability to Consent 
Assessment Team (ACAT) for evaluation to assess ongoing capacity of the subjects and to identify 
an LAR, as needed.
Please see Section 9.5.1 for consent procedure. 
9.4
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS
The potential benefit to patients undergoing this therapy would be palliation in terms of preventing 
or delaying intra-abdominal tumor progression and metastases elsewhere which can be a 
devastating and painful source of symptoms and cause for demise. In addition, significant tumor 
response may extend progression free and overall survival. The risks for this protocol include the 
risks associated with any abdominal surgery. This includes postoperative bleeding, intraabdominal 
infection, wound healing complications including fascial dehiscence, enterocutaneous fistulas, 


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anesthetic mishap and perioperative death. In addition, the toxicities of chemotherapy place the 
patients under risk. A combination of surgery and chemotherapy may decrease healing at a time 
when healing of abdominal wounds and bowel anastomosis is essential for recovery. All attempts 
will be made to avoid unnecessary enterotomies or a bowel resection where feasible. In the case 
of intra-abdominal catastrophe after surgery, patients may require reoperation.
All care will be taken to minimize risks that may be incurred by tumor sampling. However, there 
are procedure-related risks (such as bleeding, infection and visceral injury) that will be explained 
fully during informed consent. If patients suffer any physical injury as a result of the biopsies, 
immediate medical treatment is available at the NCI’s Clinical Center in Bethesda, MD. Although 
no compensation is available, any injury will be fully evaluated and treated in keeping with the 
benefits or care to which patients are entitled under applicable regulations.
9.4.1
Benefits
The potential benefit is great for these patients if a regional response is obtained. Therefore, 
although this protocol involves greater than minimal risk, it presents the prospect of direct benefit 
to individual subjects.
9.4.2
Risks
Potential complications may arise on this study from both the placement and long-term 
management of the intraperitoneal infusion system (refer to Sections 3.4 and 11.3.2) and from risks 
associated with the use of paclitaxel (11.1.2) and capecitabine (11.2.2). Protocol risks also include 
those standardly associated with abdominal laparoscopy, including pain, ileus, ascites, injury to 
organs in the abdomen (such as the intestines, stomach, bladder and blood vessels) and the 
possibility of anesthetic mishap. There may be an increased risk of wound healing or infection 
after surgery due to the use of paclitaxel and capecitabine.
9.4.2.1
Blood Sampling
Side effects of blood draws include pain and bruising, lightheadedness, and rarely, fainting.
9.4.2.2  Electrocardiogram (EKG)
This procedure is associated with minimal discomfort.
9.4.2.3
Questionnaires Risk
Questionnaires may contain questions that are sensitive in nature. The patients are asked to only 
answer questions they are comfortable with.
9.4.2.4
Tumor Biopsy 
Needle biopsy is minimally invasive and is typically a very safe procedure. Depending upon the 
site being biopsied and the type of biopsy being performed, risks can include infection of the 
biopsy site, development of a hematoma, and bleeding. Rarely more significant complications can 
occur when structures near the biopsy target are entered with the needle (e.g., puncture of lung or 
bowel). Surgical procedures for biopsy specimens will not be conducted for the sole purpose of 
research specimen collection.
9.4.2.5 Conscious Sedation
The common side effects of conscious sedation include drowsiness, delayed reflexes, hypotension, 
headache, and nausea. These are generally mild and last no more than a few hours.


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9.4.2.6 General Anesthesia
Risks of general anesthesia include temporary confusion and memory loss, although this is more 
common in the elderly, dizziness, difficulty passing urine, bruising or soreness from the IV drip, 
nausea and vomiting, shivering and feeling cold, sore throat due to the breathing tube.
9.4.2.7
Scans and Contrast 
The most common discomfort is the length of time a patient must lay still during a scan. Patients 
may also become uncomfortable with the closed space of the machines.
There is a small risk of reaction in scans involving contrast. Common reactions include pain in the 
vein where the contrast was given, a metallic or bitter taste in the mouth, headache, nausea and a 
warm or flushing feeling that lasts from 1-3 minutes. In very rare cases, severe reactions that affect 
breathing, heart rhythm or blood pressure have occurred. 
An IV catheter may need to be inserted for administration of the contrast agent or anesthetic, which 
may cause pain at the site where the IV is placed and there is a small risk of bruising or infection, 
or inflammation of the skin and vein with pain and swelling.
9.4.2.8 Risks of Exposure to Ionizing Radiation 
This research study involves exposure to radiation from 6 PET/CT scans as well as 3 CT-guided 
biopsies over the course of the first year. This radiation exposure is not required for medical care 
and is for research purposes only. Subjects will be exposed to approximately 9.6 rem. This amount 
of radiation is above the guideline of 5 rem per year, and will expose the subject to the roughly the 
same amount of radiation as 32.0 years of background radiation.
9.4.2.9
Non-Physical Risks of Genetic Research
Risk of Receiving Unwanted Information
Anxiety and stress may arise as a result of the anticipation that unwanted information regarding 
disease related DNA sequencing or disease tendencies, or misattributed paternity. Patients will be 
clearly informed that the data related to DNA sequencing and genetic analysis is coded, 
investigational, and will not be shared with patients, family members or health care providers.
Risk Related to Possibility that Information May be Released
This includes the risk that data related to genotype, DNA sequencing or risk for disease tendency 
or trait can be released to members of the public, insurers, employers, or law enforcement agencies. 
Although there are no plans to release results to the patients, family members or health care 
providers, this risk will be included in the informed consent document.
Risk to Family or Relatives
Family members or relatives may or may not want to be aware of familial tendencies or genetic 
risks of disease which may cause anxiety about possible future health problems. As previously 
noted, patients will be notified of any medically significant and actionable incidental findings. 
Study research results will not be shared with patients.
9.5
CONSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided as a physical or electronic document to the 
participant or consent designee(s) as applicable for review prior to consenting.  A designated study 


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investigator will carefully explain the procedures and tests involved in this study, and the 
associated risks, discomforts and benefits. In order to minimize potential coercion, as much time 
as is needed to review the document will be given, including an opportunity to discuss it with 
friends, family members and/or other advisors, and to ask questions of any designated study 
investigator. A signed informed consent document will be obtained prior to entry onto the study.
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance used in 
compliance with policy, including HRPP Policy 303) per discretion of the designated study 
investigator and with the agreement of the participant/consent designee(s).  Whether in person or 
remote, the privacy of the subject will be maintained. Consenting investigators (and 
participant/consent designee, when in person) will be located in a private area (e.g., clinic consult 
room). When consent is conducted remotely, the participant/consent designee will be informed of 
the private nature of the discussion and will be encouraged to relocate to a more private setting if 
needed. 
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document.  When required, witness signature will be 
obtained similarly as described for the investigator and participant.
Manual (Non-Electronic) Signature on Electronic Document:
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures:

Adobe platform (which is not 21 CFR Part 11 compliant); or,  

iMedConsent platform (which is 21 CFR Part 11 compliant) 
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the 
same screen may be used when in the same location, but is not required.  
Both the investigator and the subject will sign the document using a finger, stylus or mouse.
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent Process 
for additional information (e.g., verification of participant identity when obtaining consent 
remotely) 
found 
at: 
https://ccrod.cancer.gov/confluence/pages/viewpage.action?pageId=73203825.
 
9.5.1
Consent Process for Adults Who Lack Capacity to Consent to Research 
Participation
For participants addressed in Section 9.3, an LAR will be identified consistent with Policy 403 and 
informed consent obtained from the LAR, as described in Section 9.5.


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10 REGULATORY AND OPERATIONAL CONSIDERATIONS 
10.1 STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, the sponsor and regulatory authorities. If the study is prematurely terminated or 
suspended, the Principal Investigator (PI) will promptly inform study participants, the Institutional 
Review Board (IRB), and sponsor and will provide the reason(s) for the termination or suspension.  
Study participants will be contacted, as applicable, and be informed of changes to study visit 
schedule.
Circumstances that may warrant termination or suspension include, but are not limited to:

Determination of unexpected, significant, or unacceptable risk to participants

Demonstration of efficacy that would warrant stopping   

Insufficient compliance to protocol requirements

Data that are not sufficiently complete and/or evaluable

Determination that the primary endpoint has been met

Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, and IRB as applicable.
10.2 QUALITY ASSURANCE AND QUALITY CONTROL
The site will perform internal quality management of study conduct, data and biological specimen 
collection, documentation and completion. An individualized quality management plan will be 
developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., 
Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities.
10.3 CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 


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of this trial. The study leadership in conjunction with the National Cancer Institute has established 
policies and procedures for all study group members to disclose all conflicts of interest and will 
establish a mechanism for the management of all reported dualities of interest.
10.4 CONFIDENTIALITY AND PRIVACY
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Therefore, 
the study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible.
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical 
study site will permit access to such records.
The study participant’s contact information will be securely stored at the clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB, Institutional policies, or sponsor 
requirements.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be stored at the NCI CCR. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by the 
clinical site and by NCI CCR research staff will be secured and password protected. At the end of 
the study, all study databases will be archived at the NIH.
To further protect the privacy of study participants, a Certificate of Confidentiality has been issued 
by the National Institutes of Health (NIH). This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any civil, 
criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local 
level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research 
objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants.
11 PHARMACEUTICAL AND INVESTIGATIONAL DEVICE INFORMATION 
Paclitaxel for this study will also be used as intraperitoneally. This change in route of 
administration does not pose any increased risk compared to intravenous administration. There are 
supporting  data that clearly give information that this has been used in many patients without 
increased risk.[45]


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This clinical investigation of two marketed agents is exempt from the IND requirements because 
all of the criteria for an exemption in 21CFR 312.2(b) are met; including using an alternative route 
of administration for the paclitaxel in an unapproved indication:

The drug product is lawfully marketed in the United States.

The investigation is not intended to be reported to FDA as a well-controlled study in 
support of a new indication and there is no intent to use it to support any other significant 
change in the labeling of the drug.

In the case of a prescription drug, the investigation is not intended to support a significant 
change in the advertising for the drug.

The investigation does not involve a route of administration, dose, patient population, or 
other factor that significantly increases the risk (or decreases the acceptability of the risk) 
associated with the use of the drug product.

Additional information on clinical investigations is available on FDA's Web site at 
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm. 

The investigation is conducted in compliance with the requirements for review by an IRB 
(21 CFR part 56) and with the requirements for informed consent (21 CFR part 50).

The investigation is conducted in compliance with the requirements of 21 CFR 312.7 (i.e., 
the investigation is not intended to promote or commercialize the drug product).
11.1 PACLITAXEL (TAXOL®)
Refer to the package insert for complete information about this product.
11.1.1 Source 
Paclitaxel (Taxol®) is commercially available as a clear colorless to slightly yellow viscous 
solution. It is supplied as a nonaqueous solution intended for dilution with a suitable parenteral 
fluid prior to intravenous infusion in 5, 16.7, and 50 mL vials. (Hospira, Inc) Each mL of sterile 
nonpyrogenic solution contains 6 mg paclitaxel, 527 mg of Polyoxyl 35 Castor Oil, NF, 49.7% 
(v/v) Dehydrated Alcohol, USP and 2 mg Citric Acid, USP. It will be purchased from commercial 
sources by the NIH Clinical Center Pharmacy Department. 
11.1.2 Toxicity 
Paclitaxel has been well studied and toxicities are well defined in the package insert for this FDA 
approved drug.  The most common severe adverse reactions are related to myelosuppression and 
result in neutropenia, leukopenia and anemia.  Additionally, patients with a cardiac history must 
be monitored during first infusion due to reported conduction abnormalities resulting in AV block 
and ventricular tachycardia.  Patient with known liver disease may experience hepatic enzyme 
elevation given the high degree of hepatic metabolism.  In patients that have received oxaliplatin 
as previous therapy there is an increased risk of worsening of peripheral neuropathy.  In patients 
who have received radiation therapy there is a risk for radiation recall reactions Less severe 
reactions such as alopecia, nausea and vomiting have also been noted.  When given in an 
intraperitoneal formulation for gastric cancer the most commonly noted adverse effects were 
neutropenia and anemia.  In limited data no patients experienced abdominal pain due to 
intraperitoneal formulation.  In geriatric patients there is an overall increase in adverse events.


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11.1.3 Formulation and Preparation 
Please refer to Section 3.2.2 for details.
11.1.4 Stability and Storage 
Vials will be stored in original cartons between 20° to 25°C (68° to 77°F) per NIH Clinical Center 
Pharmacy Department protocol. Solutions for infusion prepared as recommended are stable at 
ambient temperature (approximately 25°C) and lighting conditions for up to 27 hours.
11.1.5 Administration Procedures
Please refer to Section 3.2.2 for details.
11.1.6 Incompatibilities
Refer to the package insert for complete information about this product. 
11.2 CAPECITABINE (XELODA®)
Refer to the package insert for complete information about this product.
11.2.1 Source 
Capecitabine (Xeloda®) is commercially available as biconvex, oblong film-coated tablets for oral 
administration. Each light peach-colored tablet contains 150 mg of capecitabine and each peach-
colored tablet contains 500 mg of capecitabine. (Genentech, Inc. San Francisco, CA) It will be 
purchased from commercial sources by the NIH Clinical Center Pharmacy Department.
11.2.2 Toxicity 
Capecitabine is an FDA approved medication with well-defined adverse events.  Nausea, vomiting 
and dehydration are common events which when severe may lead to dehydration, acute kidney 
injury and possible renal failure.  Additionally, bone marrow suppression has been documented 
resulting in neutropenia, anemia and thrombocytopenia.  Patients with Dihydropyrimidine 
dehydrogenase deficiency (DPD) are excluded from this study as they may experience serve and 
life-threatening adverse events due to the inability to metabolize 5-fluorouracil (5-FU).  Patients 
currently on anticoagulation therapy are at an increased risk of bleeding.  There are reports of 
increased PT and INR following initial administration of capecitabine, requiring more frequent 
PT/INR monitoring as warfarin dose adjustments.  Patients with a previous history of coronary 
artery syndrome are at increased risk of cardiotoxicity including: myocardial infarction, 
dysrhythmias, electrocardiogram changes, cardiogenic shock and sudden death.  Jaundice has been 
noted in patients with hepatic metastasis on capecitabine, but these patients will be excluded from 
this protocol.  Finally, skin reactions including toxic epidermal necrolysis, Steven Johnson 
syndrome and palmer-plantar erythrodysesthesia have been reported.
11.2.3 Formulation and Preparation 
Capecitabine 150 mg - Color: Light peach; Engraving: XELODA on one side and 150 on the other; 
150 mg tablets are packaged in bottles of 60 (NDC 0004-1100-20), individually packaged in a 
carton. 
Capecitabine 500 mg - Color: Peach; Engraving: XELODA on one side and 500 on the other; 500 
mg tablets are packaged in bottles of 120 (NDC 0004-1101-50), individually packaged in a carton.


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11.2.4 Stability and Storage 
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F); storage per NIH Clinical 
Center Pharmacy Department protocol. Capecitabine is a cytotoxic drug. Follow applicable special 
handling and disposal procedures. Any unused product should be disposed of in accordance with 
local requirements, or drug take back programs. If capecitabine tablets must be cut or crushed, this 
should be done by a professional trained in safe handling of cytotoxic drugs using appropriate 
equipment and safety procedures. 
11.2.5 Administration Procedures
Please refer to Section 3.2.3 for details.
11.2.6 Incompatibilities 
 Refer to the package insert for complete information about this product.
11.3 SUBCUTANEOUS INTRAPERITONEAL INFUSION PORT
There will be no IDE obtained for the use of the BardPort Titanium Implanted Port with Peritoneal 
Catheter in this study.
This study meets the criteria for exemption for an IDE as this investigation is not intended to 
support a new indication for use or any other significant change to the labeling; the BardPort 
Titanium Implanted Port with Peritoneal Catheter already approved and marketed and the 
investigation is not intended to support a significant change in advertising; and the investigation 
does not involve other factors that significantly increases the risks (or decreases the acceptability 
of the risks) associated with the use of this device.
11.3.1 Source 
Subcutaneous intraperitoneal infusion ports are FDA approved and commercially available 
through Bard Access Systems under the brand name BardPort Titanium Implanted Port with 
Peritoneal Catheter.  The device is made of two components, an injection port with self-sealing 
silicone septum and a radiopaque silicone rubber catheter. 
11.3.2 Possible Complications
There are potential complications with both the placement and long-term management of the 
intraperitoneal infusion system.  These include but are not limited to: 

Bleeding

Catheter or port erosion

Catheter or port occlusion

Catheter or port related sepsis

Device rotation or extrusion

Extravasation

Fibrin sheath formation

Hematoma

Intolerance reaction to implanted device

Inflammation, necrosis, scarring of skin over implanted area

Laceration of vessels or viscus


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
Perforation of vessels or viscus

Spontaneous catheter tip malposition or retraction


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13 APPENDICES
13.1 APPENDIX A: PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no 
evidence of disease.
0
Normal activity.  Fully active, 
able to carry on all pre-disease 
performance without restriction.
90
Able to carry on normal activity; 
minor signs or symptoms of 
disease.
80
Normal activity with effort; 
some signs or symptoms of 
disease.
1
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work).
70
Cares for self, unable to carry on 
normal activity or to do active 
work.
60
Requires occasional assistance, 
but is able to care for most of 
his/her needs.
2
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and 
about more than 50% of waking 
hours.
50
Requires considerable assistance 
and frequent medical care.
40
Disabled, requires special care 
and assistance.
3
In bed >50% of the time.  
Capable of only limited self-care, 
confined to bed or chair more 
than 50% of waking hours.
30
Severely disabled, 
hospitalization indicated.  Death 
not imminent.
20
Very sick, hospitalization 
indicated. Death not imminent.
4
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair.
10
Moribund, fatal processes 
progressing rapidly.
5
Dead.
0
Dead.


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13.2 APPENDIX B: CARCINOMATOSIS EXTENT EVALUATION


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13.3 APPENDIX C: ORAL MEDICATION DIARY
Today’s Date ________________________________ 
Cycle #__________
Patient Name_______________________________ (initials acceptable for patient’s name)
Patient Study ID ___________________ 
Please bring your pill bottle and this form to your physician when you go for your next appointment. 
This is required for study compliance. 
INSTRUCTIONS TO THE PATIENT: 
1. Complete one form for each cycle (14 days). 
2. You will take capecitabine tablets each day twice for 14 days followed by a 7-day rest period during 
each 3-week cycle. You should be swallowing tablet whole with water within 30 minutes after a meal. 
3. Record the date, the number of tablets you took, and when you took them. 
4. If you have any comments or notice any side effects, please record them in the Comments column. 
# tablets and 
when taken: 
Capecitabine
No pills 
(rest 
period)
Date
Week/Day
#
AM
#
PM
Comments 
Date 
Week/Day 
Comments 
W#D1 
W#D15 
W#D2 
W#D16 
W#D3 
W#D17 
W#D4 
W#D18 
W#D5 
W#D19 
W#D6 
W#D20 
W#D7 
W#D21 
W#D8 
 
W#D9 
W#D10 
 
W#D11 
 
W#D12 
W#D13 
W#D14 
Patient’s Signature: __________________________________ Date: _____________________ 
Study Team will complete this section: 
1.
Date patient started protocol treatment_____________________
2.
Date patient was removed from study ______________________ 
3.
Patient’s planned daily dose______________________________ 
4.
Total number of pills taken this month _____________________ 
Physician/Nurse Practitioner/Nurse’s Signature 
____________________________________________________________________ 


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13.4 APPENDIX D: GENERAL SPECIMEN COLLECTION REFERENCE (REFER TO OFFICIAL 
TIMEPOINTS IN PROTOCOL 13C0176)
Note: This specimen collection appendix is solely for general reference only. Official 
specimen collection timepoints for correlative studies on 13C0176 will be as indicated in 
protocol 13C0176.
The following peripheral blood will be collected for research at Baseline, Weeks 3 and 6, and at 
End of Course (unless otherwise indicated):

8 mL blood in an EDTA Lavender top tube (Baseline only, for genomic DNA);

8 mL blood in a CPT Blue/Black top tube; 

8 mL blood (plasma) in a Sodium Heparin Green top tube; 

8 mL blood (serum) in SST Gold or Marble top tube; 

8 mL blood in a Streck Cell Free DNA tube. 
Blood and urine samples will be collected at the Pre-Op visit and Follow-Up visits, 
approximately 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after the last dose of treatment 
intervention, and then every 6 months during Years 3-5, and then yearly thereafter:

8 mL blood in a Streck Cell Free DNA tube;

8 mL blood (plasma) in a Sodium Heparin Green top tube; 

8 mL blood in a CPT Blue/Black top tube; 

8 mL blood (serum) in SST Gold or Marble top tube; 

45 mL spot urine sample in a urine clean catch container.  
Peritoneal biopsy tumor tissue will be collected as available at Baseline and at End of Course for 
immunohistochemistry. 
Normal and tumor tissue, and tumor tissue with mesothelial metastases for proteogenomic 
analysis, will be collected for research during the IP port placement (see Section 3.6.2). 
Additionally, peritoneal lavage fluid collected during the operation will be sent for 
cytopathologic analysis for research purposes.