Clinical trial NCT04034251: Intraperitoneal and Intravenous Paclitaxel Chemotherapy With Oral Capecitabine for Gastric Adenocarcinoma With Peritoneal Carcinomatosis
Official title: A Phase II Study of Intraperitoneal and Intravenous Paclitaxel Chemotherapy With Oral Capecitabine for Gastric Adenocarcinoma With Peritoneal Carcinomatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Gastric Cancer
Esophagogastric Junction
Peritoneal Carcinomatosis
Keywords: Gastroesophageal Junction (Siewert III) Adenocarcinoma
Intravenous Chemotherapy
Progression Free Survival
Peritoneal Metastasis
Intraperitoneal Chemotherapy
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2019-07-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: -INCLUSION CRITERIA:

1. Patients must have histologically or cytologically confirmed gastric adenocarcinoma, including Siewert III gastroesophageal junction adenocarcinoma, confirmed by the National Cancer Institute (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. Patients may be treatment naive or have received systemic chemotherapy prior to enrollment:

   * Trastuzumab allowed as prior treatment for human epidermal growth factor receptor 2 (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.
3. Radiographic evidence of peritoneal carcinomatosis and/or sub-radiographic evidence of peritoneal carcinomatosis found at staging laparoscopy.
4. Age \>=18 years. Children under the age of 18 will not participate in this study as gastric cancer is rare in this population.
5. Eastern Cooperative Oncology Group (ECOG) performance status \<=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

   Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) \<=2.5 X institutional upper limit of normal

   creatinine \<1.5 mg/dl

   OR

   creatinine clearance \>=60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
7. Physiologically able to undergo laparoscopy and systemic chemotherapy.
8. Ability of subject to understand and the willingness to sign a written informed consent document.
9. Previous exploratory laparotomy or laparoscopy with tissue biopsy or peritoneal lavage is permitted.
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 while she or her partner is participating in this study, she should inform her treating physician immediately.
11. Patients must be co-enrolled in protocol 13C0176 (NCT01915225) and 17C0044 (NCT03027427) for sample collection.
12. Human immunodeficiency virus (HIV)-positive patients may be considered for this study only after consultation with a National Institute of Allergy and Infectious Diseases (NIAID) physician.

EXCLUSION CRITERIA:

1. Patients who are receiving any other investigational agents.
2. Previous cytoreductive surgery or intraperitoneal chemotherapy.
3. Disseminated extra-peritoneal or solid organ metastases:

   * Excludes greater omentum and ovarian metastases.
   * Radiographic signs or clinical symptoms consistent with malignant bowel obstruction.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Paclitaxel or Capecitabine or other agents used in study.
5. Previous treatment with paclitaxel or nab-paclitaxel resulting in progression of disease.
6. Existing peripheral neuropathy, Grade 3 or greater.
7. Past medical history of dihydropyrimidine dehydrogenase deficiency.
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.
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.

Primary outcomes:
measure: Progression Free Survival (PFS) in Participants With Peritoneal Metastases From Gastric Cancer After Repeated Intraperitoneal Chemotherapeutic Infusion (IPC) and Systemic Paclitaxel Administration With Concomitant Capecitabine Therapy
timeFrame: From the first treatment to progression of disease, up to 2 years and 1 month
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From first treatment until death, an average of 1.5 years
measure: Number of Grades 3-5 Serious and/or Non-serious Adverse Events Related to the Research Interventions
timeFrame: Date treatment consent signed to date off study, 18 months and 8 days; and 25 months and 10 days for the first and second group, respectively.
measure: Intra-peritoneal Progression Free Survival (iPFS) Reported With an 80% Confidence Interval
timeFrame: From the first treatment to progression of disease, up to 2 years and 1 month
measure: Intra-peritoneal Progression Free Survival (iPFS) Reported With an 95% Confidence Interval
timeFrame: From the first treatment to progression of disease, up to 2 years and 1 month
measure: Frequency of Objective Histopathologic Response to Therapy
timeFrame: At end of each course (3 treatment cycles; 9 weeks)
measure: Number of Participants With Distant Extra-peritoneal Disease-free Survival
timeFrame: From start of treatment to until time of extra-peritoneal progression, an average of 1 year
measure: Number of Participants With Intra-peritoneal Progression Free Survival (iPFS)
timeFrame: At extra-peritoneal progression, an average of 1 year
Other outcomes:
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
timeFrame: Date treatment consent signed to date off study, 18 months and 8 days; and 25 months and 10 days for the first and second group, respectively.
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Andrew Blakely, M.D.
role: PRINCIPAL_INVESTIGATOR
References: