A Phase II Trial Comparing Quality of Life After HIPEC in Patients With Stage IIIC and IV Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma
Phase: PHASE2
Conditions: Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Cancer, Stage IIIC Primary Peritoneal Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Cancer, Stage IV Primary Peritoneal Cancer
Sponsor: Wake Forest University Health Sciences

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV 
Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
1 
 
 
 
Principal Investigator: 
Name and Title 
Michael G. Kelly, MD 
Department / Section Name 
Obstetrics and Gynecology 
Email Address 
 
Phone Number 
 
 
Biostatistician: 
Name and Title 
Fang-Chi Hsu, PhD 
Department / Section Name 
Biostatistics and Data Science 
Email Address 
 
Phone Number 
 
Research Nurse: 
Name and Title 
Ashley Carroll Fansler, RN, BSN 
Email Address 
 
Phone Number 
 
Regulatory Contact: 
Name and Title 
Cindy Miller 
Email Address 
 
Phone Number 
 
 
 
 
Participating Institution(s):  
WFBCCC 
 
 
Version Date: 
 
 
04-30-2020 
Amended: 
 
 
 
05-22-2023 
03-14-2023 
 
 
 
 
 
 
 
 
 
 
 
 
Confidential
 
 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
2 
Table of Contents 
Schema ................................................................................................................................................................. 4 
1.0 
Introduction and Background .................................................................................................................... 5 
1.4 
Quality of Life ............................................................................................................................................ 6 
2.0 
Objectives ................................................................................................................................................. 6 
2.1 
Primary Objective(s) ............................................................................................................................. 6 
2.2 
Secondary Objective(s) ......................................................................................................................... 6 
3.0 
Patient Selection ....................................................................................................................................... 6 
3.1 
Inclusion Criteria ................................................................................................................................... 6 
3.2 
Exclusion Criteria .................................................................................................................................. 7 
3.3 
Inclusion of Women and Minorities ....................................................................................................... 8 
4 
Registration Procedures ........................................................................................................................... 8 
5.0 
Study Outcomes and Study Measures ..................................................................................................... 9 
5.1 
Primary Outcome .................................................................................................................................. 9 
5.2 
Secondary Outcomes............................................................................................................................ 9 
6.0 
Treatment Plan ....................................................................................................................................... 10 
6.1 
Study-Related Interventions ................................................................................................................ 10 
6.2 
Treatment Administration .................................................................................................................... 11 
6.3 
General Concomitant Medication and Supportive Care Guidelines .................................................... 12 
6.4 
Duration of Therapy ............................................................................................................................ 12 
6.5 
Duration of Follow Up ......................................................................................................................... 12 
6.6 
Criteria for Removal from Study .......................................................................................................... 13 
7.0 
Treatment Delays/Treatment Modifications ............................................................................................ 13 
7.1 
General Guidelines for Hematologic Toxicity ...................................................................................... 13 
8.0 
Measurement of Effect ............................................................................................................................ 14 
8.1 
Definitions ......................................................................................................................................... 14 
8.3 
Methods for Evaluation of Quality of Life .......................................................................................... 15 
8.2 
Quality of Life ...................................................................................................................................... 15 
8.6 
Methods for Evaluation of Survival ................................................................................................... 17 
9.0 
Adverse Events List and Reporting Requirements ................................................................................. 17 
9.1 
Adverse Event List .............................................................................................................................. 17 
9.2 
Adverse Event Characteristics ............................................................................................................ 19 
9.3 
STRC SAE Reporting Requirements .................................................................................................. 19 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
3 
9.4  
WFUHS IRB AE Reporting Requirements .......................................................................................... 20 
10.0 
Pharmaceutical Information .................................................................................................................... 20 
10.1 
Pharmaceutical Accountability ............................................................................................................ 20 
10.2 
Carboplatin .......................................................................................................................................... 20 
11.0 
Correlative Studies .................................................................................................................................. 21 
12.0 
Data Management .................................................................................................................................. 21 
13.0 
Statistical Considerations ........................................................................................................................ 22 
13.1 
Analysis of Primary Objective ............................................................................................................. 22 
13.2 
Analysis of Secondary Objective ......................................................................................................... 22 
13.3 
Power and Sample Size ...................................................................................................................... 23 
13.4 
Estimated Accrual Rate....................................................................................................................... 23 
13.5 
Estimated Study Length ...................................................................................................................... 23 
13.6 
Interim Analysis Plan .......................................................................................................................... 23 
Appendix A – Subject Eligibility Checklist ........................................................................................................... 25 
Appendix B – Protocol Registration Form ........................................................................................................... 27 
Appendix C – Mandatory STRC SAE Reporting Guidelines ............................................................................... 28 
Appendix D - SURGERY FORM ......................................................................................................................... 34 
Appendix E - PERFUSION RECORD - HIPEC Form ......................................................................................... 35 
Appendix F - FOLLOW-UP FORM ..................................................................................................................... 36 
Appendix G - MEASUREMENT FORM RECIST ................................................................................................ 37 
Appendix H - FACT-O Form ............................................................................................................................... 38 
Appendix I – FACT/GOG – AD (Abdominal Discomfort) .................................................................................... 42 
Appendix J – FACT/GOG - NTX ......................................................................................................................... 43 
Appendix K – Adverse Events Log ..................................................................................................................... 45 
 
 
 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
4 
Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRS 4-8 weeks after SOC NAC followed 
by 
Carboplatin (800 mg/m2) HIPEC after 
CRS 
Tumor assessment and follow-up 
3, 6, and 12 months 
Secondary Outcomes: 
• 
QOL by FACT-O at 3 and 6 months post-treatment 
• 
Neurotoxicity by FACT/GOG-NTX 
• 
Abdominal Discomfort by FACT/GOG-AD 
• 
Toxicities 
• 
Response rates by RECIST v1.1 
• 
Progression Free Survival 
Primary Outcome:  
QOL by FACT-O at 6 weeks post-
treatment 
Informed Consent and pre-study data 
collection 
Study enrollment 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
5 
1.0 
Introduction and Background 
 
1.1 
Ovarian Cancer 
 
Ovarian cancer is the twelfth leading cause of cancer death in the United States.1 Less than 
15% of patients are diagnosed at the local stage; for 61%, the cancer has metastasized.1 For 
these patients, 5-year survival rates are a dismal 27%.1 
 
1.2 
Cytoreductive Surgery 
 
The standard treatment for women presenting with advanced-stage ovarian cancer is surgical 
cytoreduction (CRS) and platinum-based chemotherapy agents.2  CRS is either performed 
initially or after the administration of IV chemotherapy in the neoadjuvant (NAC) setting.  
Primary CRS and NAC followed by CRS have been associated with similar survival outcomes.  
There are fewer peri-operative complications and an improved quality of life (QOL) with the NAC 
approach.  The standard first line chemotherapy agents, either after CRS or in the NAC setting, 
are platinum doublet regimens consisting of cisplatin and carboplatin with paclitaxel or 
docetaxel.2  Intraperitoneal (IP) chemotherapy has been associated with improved survival in 
three randomized controlled trials compared to IV chemotherapy after primary CRS.  However, 
IP chemotherapy has not been widely prescribed in the United States at least in part due to its 
increased toxicity and poorer QOL.  Although the response rate for these first-line therapies is 
70-80%, the majority of patients with advanced ovarian cancer will exhibit progression of their 
disease.2 
 
1.3 
HIPEC 
 
Hyperthermic intraperitoneal chemotherapy (HIPEC) is based on the rationale that 
intraperitoneal chemotherapy has a substantial pharmacokinetic advantage over systemic 
chemotherapy. The hyperthermia effects cell membranes, cytoskeletons, synthesis of 
macromolecules and DNA repair mechanisms.3 4 Furthermore, mild hyperthermia has been 
shown to potentiate the anti-tumor effects of oxaliplatin, mitomycin C (MMC), and cisplatin.5-9 
While hyperthermia has some cytostatic properties, it is the synergetic effect on 
chemotherapeutic agents which has lead most centers to utilize hyperthermia with 
chemoperfusion. The primary objective of HIPEC is to maximize drug-tumor interaction while 
minimizing systemic toxicity.  The HIPEC is delivered at the time of CRS and is a single 
treatment.  This single dose treatment offers significant advantages over conventional IP 
chemotherapy in the decrease in the number of cycles/treatment time and recovery time after 
each IP dose are avoided. 
 
The timing of peritoneal perfusion is critically important.  Extensive evidence shows that the 
effect of postoperative versus intraoperative peritoneal perfusion is reduced by the rapid 
formation of intra-abdominal adhesions as well as complications related to intra-abdominal 
catheters.9-11 Intraoperative peritoneal perfusion not only allows for the instillation of 
chemotherapeutic agents in an adhesion-free environment, it also minimizes the number of 
viable exfoliated tumor cells after resection.12-14 Taken together, this represents the biologic 
foundation for the current use of HIPEC in the treatment of advanced ovarian malignancies. 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
6 
1.4 
Quality of Life 
QOL in individuals receiving CRS plus IP chemotherapy tends to be low. Reports of QOL a year 
after HIPEC have been reported to return to near baseline levels. However, there is a lack of 
prospective studies adequately assessing QOL with CRS plus HIPEC in the area of ovarian 
cancer.  
2.0 
Objectives 
2.1 
Primary Objective(s) 
 
2.1.1 To compare the QOL in patients with advanced ovarian cancer treated with SOC NAC 
followed by CRS with HIPEC at 6 weeks post-treatment vs. QOL in patients treated with 
intravenous-therapy (IV) chemotherapy presented in Armstrong et al. (2006).   
2.2 
Secondary Objective(s) 
 
2.2.1 To describe the QOL in patients with advanced ovarian cancer treated with NAC 
followed by CRS with HIPEC at 3 and 6 months post-treatment. 
 
2.2.2 To describe neurotoxicity in patients with advanced ovarian cancer treated with NAC 
followed by CRS with HIPEC.  
 
2.2.3 To describe abdominal discomfort in patients with advanced ovarian cancer treated with 
NAC followed by CRS with HIPEC.  
 
2.2.4 To describe toxicities in patients with advanced ovarian cancer treated with NAC 
followed by CRS with HIPEC. 
 
2.2.5 To describe the response rate in patients with advanced ovarian cancer treated with 
NAC followed by CRS with HIPEC. 
 
2.2.6 To estimate progression-free survival (PFS) in patients with advanced ovarian cancer 
treated with NAC followed by CRS with HIPEC. 
3.0 
Patient Selection 
3.1 
Inclusion Criteria 
 
3.1.1 
Patients must have histologically or cytologically confirmed non-mucinous, epithelial stage 3 
or 4 carcinoma of the ovary, fallopian tube or peritoneum.  
 
3.1.2 
Patients must not have received treatment for another malignancy within 3 years of 
enrollment. 
 
3.1.3 
Patients must have received at least 3 but not more than 6 cycles of carboplatin-doublet 
based IV neoadjuvant chemotherapy and achieved at least stable disease (radiographically 
confirmed) at the conclusion of this therapy. 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
7 
3.1.4  Age ≥ 18 years.   
 
3.1. 5 
ECOG performance status ≤ 2. 
 
3.1.6 
Patients must have adequate organ and marrow function as defined below (within 30 days 
of registration): 
 
- absolute neutrophil count 
>1,500/mcL 
- platelets 
>75,000/mcL 
- total bilirubin 
≤ 1.5 mg/dL 
- creatinine clearance 
≥ 50 mL/min  
- AST(SGOT)/ALT(SGPT) 
≤ 3 X institutional upper limit of normal 
- alkaline phosphatase 
≤ 3 X institutional upper limit of normal 
 
3.1.7 
The effects of HIPEC on the developing human fetus are unknown.  For this reason, and 
because carboplatin doublet therapyconsists of pregnancy category D agents, women of 
child-bearing potential must agree to use adequate contraception (hormonal or barrier 
method of birth control; abstinence) prior to study entry and for the duration of study 
participation. Should a woman become pregnant or suspect she is pregnant while 
participating in this study, she should inform her treating physician immediately. 
 
3.1.8 
Ability to understand and the willingness to sign an IRB-approved informed consent 
document. 
 
3.2 Exclusion Criteria  
 
3.2.1 Patients may not be receiving any other investigational agents. 
 
3.2.2 Patients with extra-abdominal metastatic disease. 
 
3.2.3 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to carboplatin doublet agents. 
 
3.2.4 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. 
 
3.2.5 Pregnant women are excluded from this study because carboplatin doublet therapy consists 
of pregnancy category D agents with the potential for teratogenic or abortifacient effects. 
Because there is an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with carboplatin doublet therapy, breastfeeding should 
be discontinued. 
 
3.2.6 Men are excluded from participation due to the site-specific nature of the disease being 
studied. 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
8 
3.3 Inclusion of Women and Minorities 
 
Women of all races and ethnicity who meet the above-described eligibility criteria are eligible for 
this trial. Men are excluded from participation due to the site-specific nature of the disease being 
studied.  
 
The study consent form will also be provided in Spanish for Spanish-speaking participants. We 
plan to enroll a total of 40 individuals. Based on these study participant numbers, we expect 
approximately 3.5% of study participants to be Hispanic/Latino (N = 1). We plan to enroll at least 
15% Black or African American (N = 6), Due to population estimates and the population in the 
WFBCCC catchment area we expect no or low recruitment of American Indian/Alaska Native 
and Asian women. Should we not meet or exceed these estimates, the PI will engage the 
Cancer Center Health Equity Advisory Group to discuss strategies to enhance recruitment in 
these target populations. 
4 
Registration Procedures 
 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer control trial, must be 
linked with a protocol in EPIC within 24 hours of Informed Consent. Patients must be registered prior to the 
initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your patient: 
 
1. Complete the Eligibility Checklist (Appendix B) 
2. Complete the Protocol Registration Form (Appendix A) 
3. Alert the Cancer Center registrar by phone, and then send the signed Informed Consent Form, 
Eligibility Checklist and Protocol Registration Form to the registrar, either by fax or e-mail. 
 
 
Contact Information: 
Protocol Registrar 
 
Protocol Registrar FAX (336) 713-6772 
 
-Friday. 
 
4. Fax/e-mail ALL eligibility source documents with registration. Patients will not be registered without 
all required supporting documents. 
Note: If labs were performed at an outside institution, provide a printout of the results. Ensure that the 
most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
 
• 
assign a patient study number 
• 
register the patient on the study 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
9 
5.0 
Study Outcomes and Study Measures 
5.1 
Primary Outcome 
 
5.1.1 QOL in patients with advanced ovarian cancer treated with SOC NAC followed by 
CRS with HIPEC as determined by the FACT-O questionnaire at 6 weeks post-
treatment 
5.2 
Secondary Outcomes 
 
5.2.1 QOL in patients with advanced ovarian cancer treated with SOC NAC followed by 
CRS with HIPEC as determined by the FACT-O questionnaire at 3 and 6 months 
post-treatment 
 
5.2.2 Neurotoxicity in patients with advanced ovarian cancer treated with SOC NAC 
followed by CRS with HIPEC as determined by the FACT/GOG-NTX questionnaire 
 
5.2.3 Abdominal discomfort in patients with advanced ovarian cancer treated with SOC 
NAC followed by CRS with HIPEC as determined by the FACT/GOG-AD 
questionnaire 
 
5.2.4 Toxicities in patients with advanced ovarian cancer treated with SOC NAC followed 
by CRS with HIPEC (for one year post-op) as indicated by the number and severity of 
adverse events as defined by CTCAE v5.0 
 
5.2.5    Response rates using RECIST v1.1 criteria in patients with advanced ovarian 
cancer treated with SOC NAC followed by CRS with HIPEC – at 3, 6, and 12 months 
post surgery. 
 
5.2.6    PFS in patients with advanced ovarian cancer treated with SOC NAC followed by 
CRS with HIPEC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
10 
6.0 
Treatment Plan 
 
6.1 
Study-Related Interventions  
 
 
 
Pre-Studya 
O.R. Day 
(surgery) 
Follow-up 
Post-Treatment Visits (+/- 2 weeks) 
6 weeks 
3 Mo 
6 Mo 
12 Mo 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
Medical history 
 
X 
 
X 
X 
X 
 
X 
 
Concurrent meds 
 
X 
X 
X 
X 
X 
 
X 
 
Height, Weight, BSA 
 
X 
 
X 
X 
X 
 
X 
 
Op Note, Path Report, Perfusion Flowsheet 
 
X 
 
 
 
 
 
Adverse event evaluation 
 
 
Xd 
Xd 
 
 
 
 
Physical exam and ECOG PS 
 
X 
 
X 
X 
X 
 
X 
 
Vital signs 
 
X 
X 
X 
X 
X 
 
X 
 
B-HCGc 
X 
 
 
 
 
 
 
 
CBC w/diff, plts 
 
X 
 
 
X 
X 
X 
 
CMP 
 
X 
 
 
X 
X 
X 
CA-125 
X 
 
 
X 
X 
X 
CT of Abdomen, pelvisb 
X 
 
 
X 
X 
 
X 
FACT-O, FACT/GOG-NTX, and 
FACT/GOG-AD questionnaires 
X 
 
X 
X 
X 
 
 
a: Pre-Study visit will occur and pre-study procedures will be completed within 28 days prior to registration. 
b: CT of abdomen/pelvis as per standard-of-care. 
c: B-HCG is for women of child-bearing potential only. 
d: Adverse event monitoring will begin at time of surgery and will continue for six (6) consecutive weeks. AEs will be recorded in WISER at the 
6 week time point. 
 
 
 
 
 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
11 
6.2 
Treatment Administration 
 
6.2.1 Surgical Intervention and Subsequent Chemotherapy 
 
6.2.1.1 
Preoperative Preparation 
 
Patients will have a mechanical and antibiotic bowel preparation.  Potential 
ostomy sites will be marked by the surgeon or the endostomal nurse prior 
to surgery. 
 
6.2.1.2 
HIPEC 
 
Tumor Debulking and Establishment of Peritoneal Perfusion Circuit 
 
The HIPEC will be preceded by a complete cytoreduction to maximize its 
therapeutic benefit. The goal of cytoreduction will be resection of all gross 
tumor. A generous midline incision will be utilized for all explorations. 
Resection of the peritoneum by stripping it off the abdominal wall combined 
with multi-visceral resections (such as splenectomy, large and small bowel 
resection, hysterectomy, etc.) will be utilized for maximal tumor debulking19. 
 
Patients will be cooled to a core temperature of about 34 to 35° C by 
passive measures (i.e., not warming airway gases or intravenous solutions) 
during cytoreduction.  After the completion of cytoreductive surgery, 
peritoneal perfusion catheters will be placed percutaneously. Two inflow 
catheters (22Fr) will be directed beneath the left and right hemidiaphragms. 
One or two outflow catheters (32Fr) will be placed in the pelvis. 
Intraperitoneal catheters will be placed as per institutional standard 
practice. Temperature probes will then be placed on the inflow and outflow 
catheters. The abdominal skin incision will be temporarily closed with a 
running suture to prevent leakage of peritoneal perfusate. A perfusion 
circuit will be established with 3 L of crystalloid perfusate solution, such as 
sodium chloride, Lactated Ringers or Plasmalyte. If a perfusion circuit 
cannot be established with 3 liters a 4th liter is acceptable, but under no 
circumstances should the volume of perfusate be greater than 4 liters. Flow 
rates should be at least one liter per minute. The pelvic catheters will drain 
to a reservoir containing a coarse filter for debris and to reduce foaming. 
The heated chemotherapy solution will be added and circulated through the 
institution’s standard perfusion equipment. The temperature of the fluid in 
the patient-return and patient-directed tubing will be monitored using 
stainless steel couplers with temperature probe connectors and needle 
probes at the tips of one inflow and one outflow cannula. The abdomen will 
be gently massaged throughout the perfusion to improve drug distribution to 
all peritoneal surfaces. Constant temperature monitoring will be done at all 
temperature probes. A perfusion record will be completed during HIPEC 
(see Appendix E).  Following the perfusion, the peritoneum will be washed 
out with 3 liters of the crystalloid perfusate. 
 
HIPEC Chemotherapy Administration 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
12 
Carboplatin will be added to the perfusate once outflow temperatures 
exceed 39°C at a dose of 800 mg/m2 18.  A maximum inflow temperature of 
42.5°C is tolerated during the perfusion.  The target outflow temperature is 
40°C.  The total perfusion time after the initial addition of carboplatin will be 
90 minutes.  The carboplatin dose will be calculated based on the body 
surface area noted on admission (or as close to surgery day as possible). 
Following the perfusion, the peritoneum will be washed out with 3 liters of 
perfusate and passively drained.  The skin will then be opened, and the 
cannulas removed under direct vision. If a bowel resection is performed, 
any anastomoses may be completed before or after HIPEC; ostomies will 
be completed at the end of the entire procedure.  The abdomen will be 
inspected and the required anastomoses will be created.  The fascia and 
skin will then be closed in a standard fashion and the requisite ostomies will 
be created if necessary. 
 
6.2.1.3 
Postoperative Care 
 
The patient will be transferred to the post-anesthesia care unit for aftercare 
and then to the intensive care unit, if needed.  Early and late complications 
of surgery will be recorded in the patient’s research chart.   
 
6.3 
General Concomitant Medication and Supportive Care Guidelines 
 
Patients should receive full supportive care, including transfusions of blood and blood 
products, erythropoietin, neupogen, antibiotics, antiemetics, etc., as clinically indicated. Anti-
inflammatory or narcotic analgesics may be offered as needed. Medications considered 
necessary for the patient's well-being may be given at the discretion of the investigator, i.e., 
chronic treatments for concomitant medical conditions, as well as agents required for life-
threatening medical problems, etc. The reason(s) for treatment, dosage, and dates of 
treatment should be recorded on the flow sheets. 
 
6.4 
Duration of Therapy 
 
Therapy (HIPEC) will be administered for 90 minutes with carboplatin 800 mg/m2 during the 
surgery as described in Section 6.2.1.2 of this protocol. 
 
6.5 
Duration of Follow Up 
 
Tumor assessment for all lesions will be performed while patients are in the protocol follow-up 
phase of this study at 3, 6, and 12 months. Patients who discontinue the trial without 
documented tumor progression should be evaluated for extent of disease at the time of trial 
discontinuation.   
 
 
Patients will be followed for 30 days after the HIPEC intervention is administered for adverse 
events monitoring.  
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
13 
Patients will be followed for a minimum of 30 days after removal from study or until death, 
whichever occurs first. Patients removed from study for unacceptable adverse events will be 
followed until resolution or stabilization of the adverse event. 
6.6 
Criteria for Removal from Study 
 
Patients may withdraw/be withdrawn from the trial at any time and for any reason.  Patients 
will not be replaced. Some possible reasons for early withdrawal include the following: 
 
• 
Development of an intercurrent medical condition or need for concomitant treatment that 
precludes further participation in the trial 
• 
Unacceptable toxicity or any adverse event that precludes further participation in the trial 
• 
Study completion or discontinuation 
• 
Patient withdraws consent to continued participation in the trial 
 
The reason and date of discontinuation are to be documented in the patient’s medical record 
and in the CRF.  
 
The investigator should complete all end of treatment procedures when a patient withdraws 
from treatment.  All patients who discontinue the trial secondary to an adverse event should 
be followed until resolution, stabilization or return to a baseline condition.  All patients who 
undergo HIPEC with study agents will be included in any safety analysis. 
 
The Co-Principal Investigators may discontinue the trial at any time.  Reasons for early trial 
discontinuation may include, but are not limited to, unacceptable toxicity of study treatment, a 
request to discontinue the trial from a regulatory authority or an IRB, or poor enrollment. 
7.0 
Treatment Delays/Treatment Modifications 
 
In order to maintain dose-intensity and cumulative dose-delivery on this study, reasonable efforts will 
be made to minimize dose reduction and treatment delays as specified. Any patient whose treatment 
is delayed must be evaluated on a weekly basis until adequate hematologic and non-hematologic 
parameters have been met. No dose escalation is planned for this study. 
 
7.1 
General Guidelines for Hematologic Toxicity  
 
 
7.1.1 Treatment decisions will be based on the absolute neutrophil count (ANC) rather than 
the total white cell count (WBC). 
 
7.1.2 Lower Limits for ANC and Platelet Count:  ANC must be =>1500 and platelets 
=>75,000 to proceed with HIPEC with carboplatin 800 mg/m2.  
 
7.1.3 Use of Hematopoietic Cytokines and Protective Agents  
 
The use of hematopoietic cytokines and protective reagents are restricted as 
noted: 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
14 
7.1.3.1 
In general, patients will NOT receive prophylactic filgrastim (G-CSF), PEG-
filgrastim (Neulasta), or sargramostim (GM-CSF) unless they experience 
treatment delays or neutropenic delays or have missed or omitted doses, 
and should follow treatment modifications as specified for the following 
cycle (see Table A). However, patients may receive growth factors for 
management of neutropenic complications (e.g. neutropenic fever) in 
accordance with clinical treatment guidelines. G-CSF prophylactic 
treatment is recommended in subsequent cycles according to the tables A 
and B. Treating physicians are allowed some flexibility for treatment for 
severe neutropenia in the elderly for documented safety concerns.  
 
7.1.3.2 
Patients will NOT receive prophylactic thrombopoietic agents. 
 
7.1.3.3 
Patients may receive iron supplements and/or transfusions as clinically 
indicated for management of anemia. Treating physicians should be aware 
of the recent changes in prescribing information for the erythropoiesis 
stimulating agents (including Aranesp, Epogen and Procrit) which note that 
there is a potential risk of shortening the time to tumor progression or 
disease-free survival, and that these agents are administered only to avoid 
red blood cell transfusions. They are not indicated in patients being treated 
with curative intent. They do not alleviate fatigue or increase energy. They 
should not be used in patients with uncontrolled hypertension. They can 
cause an increased incidence of thrombotic events in cancer patients on 
chemotherapy. The updated package inserts should be consulted. 
http://www.fda.gov/Medwatch/safety/2007/safety07.htm 
 
7.2 
Unanticipated Major Surgical Procedures – (Report all surgery on the Surgery Form 
Appendix D) For any unanticipated (emergent/urgent) major surgical procedure performed for 
reasons other than disease progression treatment should be held > 28 days postoperatively. 
Treatment delay is not required for minor procedures including a) the removal or insertion of a 
central venous catheter, nephrostomy tube, or ureteral stent or b) thoracentesis or 
paracentesis for symptom relief in the absence of disease progression. 
 
 
7.3 
Cardiac Toxicity 
Symptomatic bradycardia is not an indication for routine monitoring or removal from study. 
Any arrhythmia or cardiac ischemia event should be discussed with Study Chair, and patient 
should be removed from study therapy if this is deemed necessary. 
8.0 
Measurement of Effect 
8.1 
Definitions  
 
Evaluable for toxicity.  All patients will be evaluable for toxicity after the first administration of 
chemotherapy. 
 
Evaluable for objective response.  Only those patients who have measurable disease present 
at baseline, have received one cycle of therapy, and have had their disease re-evaluated will 

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be considered evaluable for response.  These patients will have their response classified 
according to the definitions stated below.    
 
Hematologic toxicities will be recorded in accordance with the Common Terminology 
Criteria 
for Adverse Events (CTCAE) Version 5.0.  
 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 
92(3):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of 
the tumor lesions are used in the RECIST criteria. 
 
Measurable disease.  Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as >20 mm with 
conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan.  All tumor 
measurements must be recorded in millimeters (or decimal fractions of centimeters). 
 
Non-measurable disease.  All other lesions (or sites of disease), including small lesions 
(longest diameter <20 mm with conventional techniques or <10 mm using spiral CT scan), are 
considered non-measurable disease.  Bone lesions, leptomeningeal disease, ascites, 
pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, 
abdominal masses (not followed by CT or MRI), and cystic lesions are all non-measurable. 
 
Target lesions.  All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions 
in total, representative of all involved organs, should be identified as target lesions and 
recorded and measured at baseline. Target lesions should be selected on the basis of their 
size (lesions with the longest diameter) and their suitability for accurate repeated 
measurements (either by imaging techniques or clinically). A sum of the longest diameter (LD) 
for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum 
LD will be used as reference by which to characterize the objective tumor response. 
 
Non-target lesions.  All other lesions (or sites of disease) including any measurable lesions 
over and above the 10 target lesions should be identified as non-target lesions and should 
also be recorded at baseline. Measurements of these lesions are not required, but the 
presence or absence of each should be noted throughout follow-up. 
 
 
8.3 
Methods for Evaluation of Quality of Life 
The principal parameters employed to assess the QOL and symptoms are the following self-
administered questionnaires:  FACT-O (FACT-G with 27 items plus 12 items specific to ovarian 
cancer). These questionnaires are to be completed at eight time points. The primary outcome 
will address FACT-O scores, but additional assessments of abdominal pain by FACT/GOG-AD 
and neurological symptoms by FACT/GOG-Ntx.  
 
 
 
8.2 
Quality of Life 
Patient reported outcomes will be assessed at four time points: 
 
1) Once at the pre-study visit. 
2) At week 6 post-surgery 
3) At months 3 and 6 in follow-up (post-op) 

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Patients’ QOL, neurological symptoms and abdominal discomfort will be assessed with patient 
self-administered questionnaires.  
 
QOL will be measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-
O) questionnaire. The FACT-O is a multidimensional QOL questionnaire developed and 
validated for use by ovarian cancer patients; it includes 4 subscales: Physical Well-Being (7 
items), Social Well-being (7 items), Functional Well-Being (7 items), Emotional Well-Being (6 
items) and Additional Ovarian Cancer Concerns (12-items). These subscales can be analyzed 
separately or aggregated to produce a total score. The FACT-O has demonstrated reliability, 
validity, and responsiveness to change over time 31 as well as sensitivity to improvements in 
QOL experienced by patients responding to platinum/taxane therapy. The 4-item FACT/GOG-
NTX4 (neurotoxicity) subscale will be used to assess patient reported symptoms of 
neurotoxicity. The FACT-GOG/Abdominal Discomfort (AD) measure will be used to assess 
abdominal discomfort. The FACT/GOG-AD is a four item measure (two included in the FACT-
O) which measures abdominal symptoms, with average inter-item correlations of 0.64, an 
internal consistency of 0.875, and responsiveness to change over time computed on study 
data prior to the 4th cycle of chemotherapy by Huang, et al 2007.15  
 
 
 
8.5  
Methods for Evaluation of Measurable Disease 
 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All 
baseline evaluations should be performed within 90 days of registration prior to surgery. 
 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination when both methods have been used to assess 
the antitumor effect of a treatment. 
 
Clinical lesions:  Clinical lesions will only be considered measurable when they are superficial 
(e.g., palpable abdominal masses).  In the case of palpable lesions, documentation by color 
photography, including a ruler to estimate the size of the lesion, is recommended.  
 
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/or MRI:  These techniques should be performed with cuts of 5 mm or less 
in slice thickness contiguously.  Spiral CT should be performed using a 2.5 mm contiguous 
reconstruction algorithm.  This applies to tumors of the chest, abdomen, and pelvis.   
 
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.   
 
Cytology & Histology:  These techniques can be used to differentiate between partial responses 
(PR) and complete responses (CR) in rare cases (e.g., where known residual benign tumors 
can remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or stable disease is 

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mandatory to differentiate between response or stable disease (an effusion may be a side effect 
of the treatment) and progressive disease. 
 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment 
will depend on the achievement of both measurement and confirmation criteria. 
 
 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Respons
e 
Best Response for this Category 
Also Requires: 
CR 
CR 
No 
CR 
>4 wks. confirmation 
CR 
Non-CR/Non-
PD 
No 
PR 
 
>4 wks. confirmation 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
Documented at least once >4 wks. 
from baseline 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD* 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
* 
In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
 
Note: Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be reported 
as “symptomatic deterioration”.  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
8.6 
Methods for Evaluation of Survival 
 
Disease-free Survival:  Disease-free survival will be measured from the time of completion of 
treatment until the first date that recurrent or progressive disease is objectively documented 
(taking as reference for progressive disease the smallest measurements recorded since the 
treatment started). 
9.0 
Adverse Events List and Reporting Requirements 
9.1 
Adverse Event List 
 
9.1.2 Carboplatin 
 
ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN 
CANCER SWOG STUDY 
 
Carboplatin 
Arm 
Percent* 
Cisplatin 
Arm 
Percent* 
P-
Values† 

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ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN 
CANCER SWOG STUDY 
Carboplatin 
Arm 
Percent* 
Cisplatin 
Arm 
Percent* 
P-
Values† 
Bone Marrow 
Thrombocytopenia <100,000/mm3 59 
35 
< 0.001 
<50,000/mm3 22 
11 
0.006 
Neutropenia 
<2,000 
cells/mm3 
95 
97 
ns 
 
<1,000 
cells/mm3 
84 
78 
ns 
Leukopenia 
<4,000 
cells/mm3 
97 
97 
ns 
<2,000 
cells/mm3 
76 
67 
ns 
Anemia 
<11 g/dL 
88 
87 
ns 
<8 g/dL 
8 
24 
< 0.001 
Infections 
18 
21 
ns 
Bleeding 
6 
4 
ns 
Transfusions 
25 
33 
ns 
Gastrointestinal 
 
 
 
Nausea and vomiting 
94 
96 
ns 
Vomiting 
82 
91 
0.007 
Other GI side effects 
40 
48 
ns 
Neurologic 
 
 
 
Peripheral neuropathies 
13 
28 
0.001 
Ototoxicity 
12 
30 
< 0.001 
Other sensory side effects 
4 
6 
ns 
Central neurotoxicity 
23 
29 
ns 
Renal 
Serum creatinine elevations 
7 
38 
< 0.001 
Blood urea elevations 
- 
- 
- 
Hepatic 
Bilirubin elevations 
5 
3 
ns 
SGOT elevations 
23 
16 
ns 
Alkaline phosphatase elevations 29 
 
20 
ns 
Electrolytes loss 
Sodium 
- 
- 
- 
Potassium 
- 
- 
- 
Calcium 
- 
- 
- 
Magnesium 
58 
77 
< 0.001 
Other side effects 
Pain 
54 
52 
ns 
Asthenia 
43 
46 
ns 

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ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN 
CANCER SWOG STUDY 
Carboplatin 
Arm 
Percent* 
Cisplatin 
Arm 
Percent* 
P-
Values† 
Cardiovascular 
23 
30 
ns 
Respiratory 
12 
11 
ns 
Allergic 
10 
11 
ns 
Genitourinary 
11 
13 
ns 
Alopecia ‡ 
43 
57 
0.009 
Mucositis 
6 
11 
ns 
*Values are in percent of evaluable patients 
†ns = not significant, p > 0.05 
‡May have been affected by cyclophosphamide dosage delivered 
 
9.2 
Adverse Event Characteristics 
 
• 
Adverse event monitoring will begin at the time of surgery and will continue for six (6) 
consecutive weeks post-op. AE’s will be recorded in WISER at the six-week time point. 
• 
CTCAE term (AE description) and grade:  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). 
 
• 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ (see Section 7.1 above) for 
expedited reporting purposes only.   
 
• 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
9.3 
STRC SAE Reporting Requirements 
 
The Safety and Toxicity Reporting Committee (STRC) is responsible for reviewing SAEs for WFBCCC 
Institutional studies as outlined in Appendix C. STRC currently requires that all unexpected grade 4 
SAEs, all grade 5 SAEs, and any unplanned hospitalizations on these trials be reported to them for 
review. All WFBCCC Clinical Research Management (CRM) staff members assisting a Principal 
Investigator in investigating, documenting and reporting an SAE qualifying for STRC reporting are 
responsible for informing a clinical member of the STRC as well as the entire committee via the email 
notification procedure of the occurrence of an SAE.  
 
 

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9.4  
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events shall be promptly 
reported to the IRB, according to institutional policy. Reporting to the IRB is required regardless of the 
funding source, study sponsor, or whether the event involves an investigational or marketed drug, 
biologic or device. Reportable events are not limited to physical injury, but include psychological, 
economic and social harm. Reportable events may arise as a result of drugs, biological agents, 
devices, procedures or other interventions, or as a result of questionnaires, surveys, observations or 
other interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the IRB and other 
applicable parties of unanticipated problems involving risk to subjects or others. The Principal 
Investigator, however, is ultimately responsible for ensuring the prompt reporting of unanticipated 
problems involving risk to subjects or others to the IRB. The Principal Investigator is also responsible 
for ensuring that all reported unanticipated risks to subjects and others which they receive are reviewed 
to determine whether the report represents a change in the risks and/or benefits to study participants, 
and whether any changes in the informed consent, protocol or other study-related documents are 
required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the study has 
been approved by the WFUHS IRB (internal events) must be reported to the WFUHS IRB within 7 
calendar days of the investigator or other members of the study team becoming aware of the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site conducting 
the same study that has been approved by the WFUHS IRB (external events) must be reported to the 
WFUHS IRB within 7 calendar days of the investigator or other members of the study team becoming 
aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the research 
and as a result warrants a substantive change in the research protocol or informed consent 
process/document in order to insure the safety, rights or welfare of research subjects. 
10.0 Pharmaceutical Information 
 
A list of the adverse events and potential risks associated with the investigational or commercial agents 
administered in this study can be found in Section 9.1. 
10.1 Pharmaceutical Accountability 
 
Drug accountability logs will be maintained for all agents used under this protocol. These logs 
shall record quantities of study drug received and quantities dispensed to patients, including lot 
number, date dispensed, patient identifier number, patient initials, protocol number, dose, 
quantity returned, balance remaining, and the initials of the person dispensing the medication.  
10.2 Carboplatin  
 
Product description:  PARAPLATIN® (carboplatin) for Injection, USP is supplied as a sterile, 
lyophilized white powder available in single-dose vials containing 50 mg, 150 mg, and 450 mg of 

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carboplatin for administration by intravenous infusion. Each vial contains equal parts by weight 
of carboplatin and mannitol. 
 
Solution preparation: Immediately before use, the content of each vial must be reconstituted 
with either Sterile Water for Injection, USP, 5% Dextrose in Water (D5W), or 0.9% Sodium 
Chloride Injection, USP, according to the following schedule: 
 
Vial Strength 
Diluent Volume 
50 mg 
5 mL 
150 mg 
15 mL 
450 mg 
45 mL 
These dilutions all produce a carboplatin concentration of 10 mg/mL. PARAPLATIN can be 
further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% 
Sodium Chloride Injection, USP. 
 
Storage requirements: Unopened vials of PARAPLATIN are stable for the life indicated on 
the package when stored at 25°C (77°F); excursions permitted from 15°-30°C (59°-86°F) 
[see USP Controlled Room Temperature]. Protect from light.   
 
Stability:  When prepared as directed, PARAPLATIN solutions are stable for 8 hours at 
room temperature (25°C). Since no antibacterial preservative is contained in the 
formulation, it is recommended that PARAPLATIN solutions be discarded 8 hours after 
dilution. 
 
Route of administration:  PARAPLATIN is usually administered by an infusion lasting 15 
minutes or longer. No pre- or post-treatment hydration or forced diuresis is required. 
Parenteral drug products should be inspected visually for particulate matter and 
discoloration prior to administration. 
 
Disposal: Caution should be exercised in handling and preparing PARAPLATIN (carboplatin) 
for Injection, USP. Several guidelines on this subject have been published. To minimize the risk 
of dermal exposure, always wear impervious gloves when handling vials containing 
PARAPLATIN (carboplatin) for Injection, USP. If PARAPLATIN (carboplatin) for Injection, USP 
or solutions containing PARAPLATIN (carboplatin) for Injection, USP contact the skin, 
immediately wash the skin thoroughly with soap and water. If PARAPLATIN (carboplatin) for 
Injection, USP or solutions containing PARAPLATIN (carboplatin) for Injection, USP contact 
mucous membranes, the membranes should be flushed immediately and thoroughly with 
water. 
11.0 Correlative Studies 
None 
12.0 Data Management 
 
The Appendices contain master copies of the case report forms (CRFs) to be used for this protocol. 
 
Note: If the patient does not have protocol therapy at surgery, it is still necessary to submit Day 0 data 
and the No HIPEC Follow-Up form annually. 
Informed consent document 
EPIC 

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Protocol Version Date: 05/22/2023 
 
 
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Protocol registration Form (Appendix B) 
WISER 
FACT-O, FACT-GOG-NTX4, FACT/GOG-AD (Appendices H, I, J) 
WISER 
Follow-up form (Appendix F) 
WISER 
RECIST measurement form (Appendix G) 
WISER 
Adverse Events Log (Appendix K) 
WISER 
 
The Protocol Registration Form and signed Informed Consent Form should be completed and faxed to 
the WFBCCC Registrar in order to enroll and randomize participants.  All other CRFs & supporting 
documents should be faxed to the attention of the Study Coordinator according to the following 
schedule: 
 
Form 
Submission Schedule 
Surgery Form 
Form and reports within 30 days of surgery 
Perfusion Record - HIPEC Form 
Form within 30 days of surgery 
Adverse Event Log 
Form within 7 days of completion of time period. 
Follow-Up / Measurement Form 
Form and supporting documents within 7 days of 
mo. 3, 6, and 12 
FACT-O, FACT/GOG-AD, FACT/GOG-
NTX 
Prestudy, , Week 6, months 3 and 6 post-
treatment (follow-up) 
13.0 Statistical Considerations 
 
13.1 Analysis of Primary Objective 
 
This is a descriptive study. The primary objective is to compare the QOL in patients with 
advanced ovarian cancer treated with SOC NAC followed by CRS with HIPEC vs. QOL in 
patients treated with IV chemotherapy at 6 weeks post-treatment presented in Armstrong et al. 
(2006). Only the patients treated with SOC NAC followed by CRS with HIPEC will be recruited 
in this study.  The summary data of QOL for patients treated with IV chemotherapy collected in 
Armstrong et al. (2006) will be directly used. The same as Armstrong et al., QOL will be 
measured using the Fact-O questionnaire and treatment as a continuous outcome. The 
distribution of QOL at 6 weeks post-treatment will be examined.  The descriptive statistics such 
as mean, standard deviation, median and interquartile range will be calculated.  One sample t-
test will be used to compare the mean QOL in the study sample to the mean QOL based on 
Armstrong et al. 
 
13.2 Analysis of Secondary Objective 
 
13.2.1 To describe QOL in patients with advanced ovarian cancer treated with SOC NAC 
followed by CRS with HIPEC as determined by the FACT-O questionnaire at 3 and 6 months 
post-treatment, the distribution of QOL at 3 and 6 months post-treatment will be examined.  The 
descriptive statistics of QOL at 3 and 6 months post-treatment will be presented. In addition, the 
longitudinal data of QOL over time will be displayed graphically with individual trajectories.  
 
13.2.2. To describe neurotoxicity at the end of study, the descriptive statistics will be presented. 
Since neurotoxicity is a 4-item measure from FACT/GOG-NTX4, counts and percentages will be 
calculated. Mean and standard deviation will be also calculated. 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
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13.2.3. To describe abdominal discomfort at the end of study, the descriptive statistics will be 
presented. The abdominal discomfort is a 4-item score from FACT-GOG/AD.  Counts and 
percentages will be calculated. Mean and standard deviation will be also calculated. 
 
13.2.4. The toxicities will be measured by the number and severity of adverse events defined by 
CTCAE v5.0. Counts and percentages will be calculated for each adverse event. Mean, 
standard deviation, median, and interquartile range will be calculated for number of adverse 
events. 
 
13.2.5. The response rate using RECIST criteria at each time point will be estimated. Counts 
and percentages will be calculated. 
 
13.2.6. This secondary objective is to estimate progression free survival using survival analysis. 
Survival will be measured up to the time until progression, date of last contact, or death, 
whichever comes first. Kaplan-Meier survival curves will be used to estimate the survival 
probabilities.  The survival probabilities for the whole sample and for the stratified groups 
(weekly or 3-weekly) will be calculated. The log-rank test will be used to compare the two 
stratified groups. 
13.3 Power and Sample Size 
The power calculation is performed to test the primary objective. It is calculated to compare the 
mean QOL between the study patients and the mean QOL from Armstrong et al. (2006). Based 
on Armstrong et al., the standard deviation of QOL at 6 weeks post treatment is 19.2. Fifty 
patients will be recruited. The dropout rate is anticipated to be very small, around 1 to 2% at 6 
weeks post treatment. Assuming 80% power, a two-sided test and a significance level of 20%, 
the minimal detectable difference of QOL between the study sample and Armstrong et al. is 5.9. 
If assuming a higher dropout rate, say 10% at 6 weeks post treatment, the minimal detectable 
difference for QOL is 6.1. Based on Armstrong et al., the mean difference of QOL between the 
two standard treatments (IV vs. intraperitoneal) is 5.2. We assume that the mean difference 
between HIPEC and IV can be larger.  However, we are also aware that we may not have 
enough power to detect the difference.  This study is for the descriptive purpose.  The data 
collected in this study can be very useful for future research. 
 
13.4 Estimated Accrual Rate 
Accrual is expected to be 40 patients in 18 months. Targeted accrual should be met within 1 ½ 
years. Under the current amendment (Protocol Version Date: 03/14/2023), an additional 10 
patients will be recruited at an accrual rate of 1 patient per month.  
 
13.5 Estimated Study Length 
The total study length is approximately 3 years. The estimated study length for the current 
amendment (Protocol Version Date: 03/14/2023) is approximately 2 years.  
 
13.6 Interim Analysis Plan 
Interim reviews will be performed at 6 weeks, 3 and 6 months post-treatment to assess accrual, 
retention, the incidence of AEs and SAEs.  
 
  

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
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Huang HQ, Brady MF, Cella D, Fleming G. Validation and reduction of FACT/GOG-Ntx subscale for 
platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol 
Cancer. 2007;17(2):387-393. 
16. 
Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. The 
New England journal of medicine. 2006;354(1):34-43. 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
25 
Appendix A – Subject Eligibility Checklist 
 
IRB Protocol No. 00044434 
CCCWFU Protocol No. 83216 
Study Title: A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, 
Fallopian Tube or Primary Peritoneal Carcinoma 
Principal Investigator:  Michael Kelly, M.D. 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to 
Confirm * 
Patients must have histologically or 
cytologically confirmed non-mucinous, 
epithelial stage 3 or 4 carcinoma of the ovary, 
fallopian tube or peritoneum. 
□ 
□ 
 
Patients must not have received treatment for 
another malignancy within 3 years of 
enrollment 
□ 
□ 
 
Patients must have received at least 3 but not 
more than 6 cycles of carboplatin-doublet 
based IV chemotherapy AND achieved at 
least stable disease (radiographically 
confirmed) at the conclusion of this therapy. 
□ 
□ 
 
Age ≥18 years 
□ 
□ 
 
ECOG performance status ≤ 2. 
□ 
□ 
 
Patients must have adequate organ and 
marrow function as defined below 
(within 30 days of registration): 
 
-absolute neutrophil count >1,500/mcL 
-platelets >75,000/mcL 
-total bilirubin ≤ 1.5 mg/dL 
- creatinine clearance   ≥ 50 mL/min 
-AST(SGOT)/ALT(SGPT) ≤ 3 X institutional 
upper limit of normal 
-alkaline phosphatase ≤ 3 X institutional upper 
limit of normal 
 
□ 
□ 
 
The effects of HIPEC on the developing 
human fetus are unknown.  For this reason, 
and because carboplatin doublet therapy 
consists of pregnancy category D agents, 
women of child-bearing potential must agree 
to use adequate contraception (hormonal or 
barrier method of birth control; abstinence) 
prior to study entry and for the duration of 
study participation. Should a woman become 
pregnant or suspect she is pregnant while 
participating in this study, she should inform 
her treating physician immediately. 
□ 
□ 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
26 
Ability to understand and the willingness to 
sign an IRB-approved informed consent 
document  
□ 
□ 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to 
Confirm * 
 
 
 
 
Patients may not be receiving any other 
investigational agents. 
□ 
□ 
 
Patients with extra-abdominal metastatic 
disease 
□ 
□ 
 
History of allergic reactions attributed to 
compounds of similar chemical or biologic 
composition to carboplatin doublet agents. 
□ 
□ 
 
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 
□ 
□ 
 
Pregnant women are excluded from this study 
because carboplatin doublet therapy consists 
of pregnancy category D agents with the 
potential for teratogenic or abortifacient 
effects. Because there is an unknown but 
potential risk for adverse events in nursing 
infants secondary to treatment of the mother 
with carboplatin doublet therapy, 
breastfeeding should be discontinued 
□ 
□ 
 
Men are excluded from participation due to 
the site-specific nature of the disease being 
studied 
□ 
□ 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
WISER Assigned PID: __________________ 
 
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility:_______________________ Date: __ __/__ __/__ __ 
 
Signature of Treating Physician:    _____________________________________ Date:  __ __/__ __/__ __ 
 
Signature of Principal Investigator**:  _____________________________________ Date:  __ __/__ __/__ __ 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, 
specifically state which document in the medical record was used to assess eligibility. Also include the date on the 
document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
**Principal Investigator signature can be obtained following registration if needed 
 
 

A Phase II Trial Evaluating Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian 
Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
CCCWFU 83216 
 
Protocol Version Date: 05/22/2023 
 
 
27 
Appendix B – Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: _____________________ First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
 
 
Ethnicity (choose one):   Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
 
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Registrar can be contacted by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Completed Eligibility Checklist and Protocol Registration Form must be hand delivered, faxed or e-mailed to the registrar at 
. 
 
 
 
 
 
 
 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
 YES   NO 
 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by WISER): 
___ ___ ___ ___ ___ ___ ___ ___ 
 

 
 
 
Protocol version date 03-14-23 
 
 
 
 
 
 
 28  
 
Appendix C – Mandatory STRC SAE Reporting Guidelines 
 
Safety and Toxicity Review Committee (STRC)  
Serious Adverse Event (SAE) Notification SOP 
     Date: 07/10/2019 
 
 
Mandatory STRC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC Investigator 
Initiated interventional trials to the Safety and Toxicity Review Committee (STRC). A trial is 
considered a WFBCCC Investigator Initiated interventional trial if the following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the Wake Forest 
University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation and/or monitoring 
of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research Categories 
definitions provided by the NCI in the Data Table 4 documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based on where 
patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all patients are 
enrolled from one of the WFBCCC sites. These include the main outpatient Cancer Center clinics 
(located in Winston-Salem) as well as WFBCCC affiliate sites located in Bermuda Run (Davie 
Medical Center), Clemmons, Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials where patients 
are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program (NCORP) that are 
conducted at multiple sites where the PI is a member of a department at the Wake Forest 
University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the PI is a member of 
a department at the Wake Forest University Baptist Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the PI is a member 
of a department at the Wake Forest University Baptist Medical Center. 
 
All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients enrolled on 
WFBCCC Investigator Initiated Interventional trials must be entered into the WISER system. The only 
exception to this requirement is for patients enrolled on NCORP trials at non- WFBCCC sites. AEs and 
SAEs for NCORP patients enrolled at WFBCCC sites must be entered into the WISER system. Once 
these AEs and SAEs are entered in WISER, certain actions must be taken regarding the reporting of 
specific Adverse Events to the STRC. 
 
All Adverse Events that occur during protocol intervention (defined below) and are coded as either 1) 
unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours (regardless of grade), or 
grade 5 (death) must be reported to the STRC using the using the SAE console in WISER. 
 
A research nurse or clinical research coordinator when made aware that an adverse event meets one of 
the above criteria has occurred on a WFBCCC Investigator Initiated interventional trial, is responsible for 
informing a clinical member of the STRC by phone (or in-person) about the adverse event. The 

 
 
 
Protocol version date 03-14-23 
 
 
 
 
 
 
 29  
 
nurse/coordinator should contact the treating physician prior to calling the STRC clinical member to obtain 
all details of the SAE, as well as all associated toxicities to be recorded along with the SAE. In addition, 
this nurse or coordinator is responsible for entering the adverse event information into the SAE console in 
WISER.  Once the adverse event has been entered into the SAE console an email informing the entire 
STRC committee will be generated. 
 
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team for a WFBCCC 
Institutional Interventional trial. Ultimately, the protocol PI has the primary responsibility for AE 
identification, documentation, grading and assignment of attribution to the investigational 
agent/intervention. However, when an AE event as described above is observed, it is the 
responsibility of the person who observed the event to be sure that it is reported to the STRC. 
 
What is considered during protocol intervention? 
During protocol intervention is considered to be the time period while a patient is on study treatment or 
during the time period within 30 days of last study treatment (even if patient begins a new (non-study) 
treatment during the 30 days). This window of 30 days should be the standard window to be used in all 
protocols unless a specific scientific rationale is presented to suggest that a shorter window can be used 
to identify events. If it is a trial sponsored by Industry and the sponsor requires a longer window for 
monitoring of SAEs, then the longer window of time specified by the sponsor should be followed. 
 
What is considered as an Unexpected Grade 4 event? 
Any grade 4 event that was not specifically listed as an expected adverse event in the protocol should be 
considered as unexpected. A grade 4 adverse event can be considered to be unexpected if it is an event 
that would not be expected based on the treatment being received or if it is unexpected based on the 
health of the patient. In either case, if there is any uncertainty about whether a grade 4 adverse event is 
expected or unexpected it should be reported to STRC. 
 
 
STRC notification responsibilities of the person (e.g., nurse) handling the reporting/documenting of 
the SAE in WISER: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the STRC as listed 
below (page if necessary) 
2. Enter a new SAE into the SAE module that is located in the Subject>> CRA Console in WISER 
WITHIN 24 HOURS of first knowledge of the event. Information can be entered and saved, but the 
STRC members will not be notified until a date is entered into the STRC Notification Date Field. 
This will ensure that all persons that need to be made aware of the event (i.e., study team 
members and STRC members) will be notified; remember to file a copy of the confirmation. 
3. Document that the appropriate person(s) on the STRC has been contacted. Indicate the name of 
the STRC clinician that was contacted in the Event Narrative field in the SAE console of the 
particular subject. 
1. Document whether or not the protocol should be suspended based on the discussion with the 
STRC clinician. This is the major function of the email notification. Enter whether the protocol 
should be suspended in the Event Narrative Field. 
2. Follow up/update the clinical member(s) of STRC regarding any new developments or information 
obtained during the course of the SAE investigation and reporting process. 
 
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen Shot 3): 
1. Event Date 
2. Reported Date 
3. Reported by 
4. If Grade 5, enter Death Date 

 
 
 
Protocol version date 03-14-23 
 
 
 
 
 
 
 30  
 
5. If Grade 5, enter Death occurred: within 30 days 
6. Event Narrative: Brief description (include brief clinical history relevant to this event, including 
therapies believed related to event). Begin narrative with the STRC clinician who was notified and 
Date/Time notified. In addition, state attribution by STRC clinician as either “Unrelated”, “Unlikely”, 
“Possibly”, “Probably”, or “Definitely”.  Always include the following here: 
i. 
STRC clinician name and comments 
ii. Date of last dose before the event 
iii. Is suspension of the protocol needed? Y/N 
7. Treating Physician comments 
8. PI comments, if available 
9. Protocol Attribution after discussion with STRC clinician 
10. Outcome (Fatal/Died, Intervention for AE Continues, Migrated AE, Not Recovered/Not Resolved, 
Recovered/Resolved with Sequelae, Recovered/Resolved without Sequelae, Recovering and 
Resolving) 
11. Consent form Change Required? Y/N 
12. SAE Classification *This is required in order for the email notification to be sent* 
13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. 
Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. 
Action 
j. 
Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
 
14. Enter Date Notified STRC -- *This is required for the email notification to be sent* 
 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. If you do not 
receive an email within 5 minutes, check that you have entered the “Date Notified STRC” and the 
“SAE Classification”. If these have been entered and the email still has not been received, take a 
screen shot of the SAE in WISER and immediately email it out to all of the STRC members listed in 
this SOP. In the subject line, indicate that this is a manual transmission of the SAE in lieu of the 
auto-generated email. It is required that a notification goes to the STRC members immediately so 
that their assessment can be obtained within the 24 hour time frame requirement. Contact the 
Cancer Center Programmer/Analyst to alert that there is an issue with the auto-generated email. 
 
 
 

 
 
 
Protocol version date 03-14-23 
 
 
 
 
 
 
 31  
 
The Clinical Members of STRC to Notify by Phone or Page: 
 
  
 
 
        
 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone call or page 
within 30 minutes, then initiate contact with a different STRC clinician. Allow up to 30 minutes for the new 
STRC clinician to respond to a phone call or page before contacting another member. These times (30 
minutes) are a general guideline. Best judgment as a clinical research professional should be used giving 
considerations of the time of day, severity of the SAE, and other circumstances as to when it is 
appropriate to contact backup clinicians. If the event occurs near the end of day, then leave messages 
(voice or email) as appropriate and proceed with submitting the STRC notification form. It is important to 
take reasonable steps and to document that some type of contact has been initiated to one or more of the 
clinical members of STRC. 
 
STRC CLINICAN RESPONSIBILITY: 
It is the responsibility of the STRC clinician to review all reported events, evaluate the events as they are 
reported; and communicate a response to the Investigator, event reporter and the members of STRC. The 
review will include but not be limited to the information reported; there may be times when additional 
information is needed in order for an assessment to be made and further communication directly with the 
investigator may be warranted. STRC reserves the right to disagree with the Investigator's assessment. If 
STRC does not agree with the Investigator, STRC reserves the right to suspend the trial pending further 
investigation. If there is any immediate danger or harm that could be present for a future patient based on 
the information provided in the STRC report then an immediate suspension of enrollment should be 
considered. 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional information is 
available do not submit a new report. Rather, go to the original email that was sent to the STRC and 
using that email “reply to all”. Entitle this new email “Amendment for (list date of event and patient ID)” 
this will avoid duplications of the same event. List the additional information being reported. This 
information needs to be entered into WISER as well. To do this, go to the Subject console and click 
SAEs on the left column. Click on the appropriate SAE number that needs updating. Then click update. 
This will allow additional information to be added 
 
Acronyms 
AE – Adverse Event 
STRC-Safety and Toxicity Review Committee 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
 
 
 
 

 
 
 
Protocol version date 03-14-23 
 
 
 
 
 
 
 32  
 
Screen Shots: 
 
The following screen shots come from the SAE Console within the Subject Console in WISER. 
 
Screen Shot 1: 
 
Screen Shot 2: 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
33  
 
Screen Shot 3:
 
 
 
Screen Shot 4: 
 
 
 
 
 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
34  
 
Appendix D - SURGERY FORM    
 
 
 
FAX # 336-716-4334 
 
Patient Initials;____________  
 
Study ID# 83216 
Institution:________________  
 
Surgeon ________________ 
 
DATE of SURGERY__ __/__ __/__ __  
 
What was the BSA value that the dose was based on?: ______m2   Weight____  Height____ 
 
• 
What is the Resection Status after surgery? (circle)       R0  R1  R2a  R2b   R2c 
• 
What was the duration of HIPEC perfusion in minutes?  ________________min. 
• 
What is the average Inflow / Outflow temperature (C0)? I   ________ / _______ 
• 
What was the length of surgical procedure from start to end? ____________ hours 
 
Does the Operative Report accompany this form?____ YES  _____NO 
 
 
 
If not, note reason: 
______________________________________________________________________ 
 
______________________________________________________________________ 
 
Does the Pathology report accompany this form?____ YES _____NO 
 
 
 
If not, note reason: 
______________________________________________________________________ 
 
______________________________________________________________________ 
 
Does the Perfusion Record – HIPEC flowsheet accompany this form? 
____ YES  ____NO 
 
 
 
If not, note reason: 
______________________________________________________________________ 
 
______________________________________________________________________ 
COMMENTS: 
____________________________________________________________________________________
____________________________________________________________________________________
__________________________________________________________________ 
 
 
Person Completing Form ___________________________ 
DATE __ __/__ __/___ ___ 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
35  
 
Appendix E - PERFUSION RECORD - HIPEC Form    
 
 
FAX # 336-716-4334 
 
Patient Initials;____________   Study ID# 83216 
DATE of SURGERY__ __/__ __/__ __ 
 
Institution:_______________ Surgeon: __________Perfusate: _______________ 
Perfusate Volume (L): ________ 
 
*Average Perfusate IN/OUT Temp: _________/_________        (*) Required fields 
 
*Time 
Event Time 
Flow 
Temperatures 
H2O 
Perfusate 
In 
Perfusate 
Out 
Patient 
 
0 minutes 
*Carboplatin 
*Dose:________ 
 
 
 
 
 
 
15 minutes 
 
 
 
 
 
 
30 minutes 
 
 
 
 
 
 
45 minutes 
 
 
 
 
 
 
60 minutes 
Dose:________ 
 
 
 
 
 
 
75 minutes 
 
 
 
 
 
 
90 minutes 
 
 
 
 
 
 
105 minutes 
 
 
 
 
 
 
120 minutes 
 
 
 
 
 
 
 
Completed by:___________________________________ 
Date: __ __/__ __/__ __ 
 
 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
36  
 
Appendix F - FOLLOW-UP FORM  
 
 
 
FAX # 336-716-4334  
 
 
 
 
 
 
Page 1of 1 
Patient initials (Last, First): ________________    Medical Record#: __ __ __ __ __ __ __ __  
Institution: _____________________________     Study number: 83216 
 
☐HIPEC 
 
 
⁯___  6 Week 
___  3 month 
 
⁯   
⁯___  6 month 
 
⁯___ 12 month (PROs not filled out at this visit) 
 
 
*Please check visit and complete the rest of this form according to that protocol visit* 
 
Physical Exam/ vital signs DATE:  __ __/__ __/__ __ (ECOG) Performance status_______ 
 
Was the FACT – O Questionnaire completed?    Yes ____    No ____    N/A____       
                                                                                          DATE:  __ __/__ __/__ __ 
 
**Fax questionnaire along with this form. 
 
Was the CT/MRI or CXR of chest, abdomen, pelvis done?  ____Yes ____No ____ N/A             
DATE:  __ __/__ __/__ __ 
**Fax CT/MRI report along with this form. 
 
Were LABS completed? _____ Yes_____ No  
 
CBC with Diff. 
YES 
NO 
N/A 
DATE   __ __/__ __/__ __ 
 
Serum Chemistry 
YES 
NO 
N/A 
DATE   __ __/__ __/__ __ 
 
Tumor Markers 
YES 
NO 
N/A 
DATE   __ __/__ __/__ __ 
 
**FAX LAB reports along with this form. 
 
CURRENT DISEASE STATUS 
 
EVIDENCE OF PROTOCOL RELATED CANCER: 
____ YES 
____ NO                         
 
 PROGRESSION: ____ YES    _____NO  (If first report of progression, complete the Measurement Form 
& attach: *No further report needs completed after the first report of progression.) 
 
DEATH 
 
DATE OF DEATH: _______________________     
CAUSE OF DEATH: 
____ CANCER   ____ DRUG____SURGERY 
COMPLICATIONS_______________ OTHER (Specify): 
____________________________________________________________________________ 
Person Completing Form ___________________Date completed __ __/__ __/__ __ 
 
 
 
 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
37  
 
Appendix G - MEASUREMENT FORM RECIST  
      
 
 
 
 
Target Lesions 
TARGET Lesions 
Lesion 
Site 
Imaging 
(ie,CT, MRI) 
Baseline 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
Cycle_____ 
Date: 
(Se, Im) 
01 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
02 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
03 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
04 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
05 
 
 
 
mm 
mm 
mm 
mm 
mm 
mm 
Sum of Diameters 
mm 
mm 
mm 
mm 
mm 
mm 
% Change (% ∆)  from Baseline or Nadir* & absolute 
value (AbV) 
 
NA 
        
          NA 
% ∆ 
                       
        AbV 
 
 
 
 
Target Lesion Response 
      N/A 
 
 
 
 
 
 
Non-Target Lesions 
NON-TARGET Lesions 
Lesio
n 
Site 
Imaging 
Baseline 
Cycle_____ 
Cycle_____ 
Cycle_____ 
Cycle_____ 
Cycle_____ 
01 
 
 
 
 
 
 
 
 
 
02 
 
 
 
 
 
 
 
 
 
03 
 
 
 
 
 
 
 
 
 
04 
 
 
 
 
 
 
 
 
 
05 
 
 
 
 
 
 
 
 
 
Non-Target Lesion Response 
N/A 
 
 
 
 
 
 
New Lesions 
New 
1 
 
 
 
 
N/A 
 
 
 
 
 
2 
 
 
 
 
N/A 
 
 
 
 
 
3 
 
 
 
 
N/A 
 
 
 
 
 
Overall Tumor Response 
 
 
 
 
Cycle___ 
 
Cycle___ 
 
Cycle___ 
 
 
Cycle___ 
 
 
Cycle___ 
 
    
 
 
 
 
 
Radiologist Signature: 
 
 
 
 
 
 
Treating Physician Signature: 
 
 
 
 
 
 
PI Signature: 
 
 
 
 
 
 
 
Completed By:___________________________________ Signature of Principal Investigator* _______________________ 
Date Completed: __ __/__ __/__ __  
 
Date Completed __ __/__ __/__ __ 
(*Signature needed for Assignment of Final Response at time of progression or End of Study)  

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
38  
 
Appendix H - FACT-O Form 
 
Study Number: 83216 
 
PID:  __ __ __ __ __ __ __ __ 
 
Investigator: Michael Kelly, M.D. 
Date: __ __/__ __/__ __ 
 
 
Below is a list of statements that other people with your illness have said are important. Please circle or 
mark one number per line to indicate your response as it applies to the past 7 days. 
 
 
PHYSICAL WELL-BEING 
 
Not at 
all 
A little 
bit 
Some-
what 
Quitea 
bit 
Very 
much 
 
GP1 
I have a lack of energy
 ..................................................................................................  
0 
1 
2 
3 
4 
GP2 
I have nausea
 ..................................................................................................  
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have trouble meeting the 
needs of my family
 ..................................................................................................  
 
0 
 
1 
 
2 
 
3 
 
4 
GP4 
I have pain
 ..................................................................................................  
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment
 ..................................................................................................  
0 
1 
2 
3 
4 
GP6 
I feel ill
 ..................................................................................................  
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not at 
all 
A little 
bit 
Some-
what 
Quitea 
bit 
Very 
much 
 
GS1 
I feel close to my friends
 ..................................................................................................  
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family
 ..................................................................................................  
0 
1 
2 
3 
4 
GS3 
I get support from my friends
 ..................................................................................................  
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness
 ..................................................................................................  
0 
1 
2 
3 
4 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
39  
 
 
Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
 
 
EMOTIONAL WELL-BEING 
Not at 
all 
A little 
bit 
Some-
what 
Quitea 
bit 
Very 
much 
 
GE1 
I feel sad
 ..................................................................................................  
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with my illness
 ..................................................................................................  
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my illness
 ..................................................................................................  
0 
1 
2 
3 
4 
GE4 
I feel nervous
 ..................................................................................................  
0 
1 
2 
3 
4 
GE5 
I worry about dying
 ..................................................................................................  
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse
0 
1 
2 
3 
4 
 
 
 
 
FUNCTIONAL WELL-BEING 
 
Not at 
all 
A little 
bit 
Some-
what 
Quitea 
bit 
Very 
much 
 
GF1 
I am able to work (include work at home)
 ..................................................................................................  
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is fulfilling
 ..................................................................................................  
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication about my illness
 ..................................................................................................  
 
0 
 
1 
 
2 
 
3 
 
4 
GS6 
I feel close to my partner (or the person who is my main 
support)
 ..................................................................................................  
 
0 
 
1 
 
2 
 
3 
 
4 
Q1 
Regardless of your current level of sexual activity, please answer 
the following question. If you prefer not to answer it, please mark 
this box           and go to the next section. 
 
 
 
 
 
GS7 
I am satisfied with my sex life
..................................................................................................
0 
1 
2 
3 
4 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
40  
 
GF3 
I am able to enjoy life
 ..................................................................................................  
0 
1 
2 
3 
4 
GF4 
I have accepted my illness
 ..................................................................................................  
0 
1 
2 
3 
4 
GF5 
I am sleeping well
 ..................................................................................................  
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun
 ..................................................................................................  
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life right now
0 
1 
2 
3 
4 
 
 
 
Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
 
 
ADDITIONAL CONCERNS 
 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
 
 
O1 
I have swelling in my stomach area
 ..................................................................................................  
0 
1 
2 
3 
4 
C2 
I am losing weight
 ..................................................................................................  
0 
1 
2 
3 
4 
C3 
I have control of my bowels
 ..................................................................................................  
0 
1 
2 
3 
4 
O2 
I have been vomiting
 ..................................................................................................  
0 
1 
2 
3 
4 
B5 
I am bothered by hair loss
 ..................................................................................................  
0 
1 
2 
3 
4 
C6 
I have a good appetite
 ..................................................................................................  
0 
1 
2 
3 
4 
C7 
I like the appearance of my body
 ..................................................................................................  
0 
1 
2 
3 
4 
BMT5 
I am able to get around by myself
 ..................................................................................................  
0 
1 
2 
3 
4 
B9 
I am able to feel like a woman
 ..................................................................................................  
0 
1 
2 
3 
4 
O3 
I have cramps in my stomach area
 ..................................................................................................  
0 
1 
2 
3 
4 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
41  
 
BL4 
I am interested in sex
 ..................................................................................................  
0 
1 
2 
3 
4 
BMT7 
I have concerns about my ability to have children
 ..................................................................................................  
0 
1 
2 
3 
4 
 
 
END OF FACT-O 
 
 
 
 
 
 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
42  
 
Appendix I – FACT/GOG – AD (Abdominal Discomfort) 
 
Study Number: 83216 
 
PID:  __ __ __ __ __ __ __ __ 
 
Investigator: Michael Kelly, M.D. 
Date: __ __/__ __/__ __ 
 
Please circle or mark one number per line to indicate your response as it 
applies to the past 7 days. 
 
 
 
ADDITIONAL CONCERNS 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
AD1 
I have pain
 ................................................................................  
0 
1 
2 
3 
4 
AD2 
I have cramps in my stomach area
 ................................................................................  
0 
1 
2 
3 
4 
AD3 
I have pain in my stomach area
 ................................................................................  
0 
1 
2 
3 
4 
AD4 
Stomach pain interferes with my daily functioning 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
43  
 
Appendix J – FACT/GOG - NTX 
 
Study Number: 83216 
 
PID:  __ __ __ __ __ __ __ __ 
 
Investigator: Michael Kelly, M.D. 
Date: __ __/__ __/__ __ 
 
Below is a list of statements that other people with your illness have said are 
important. Please circle or mark one number per line to indicate your 
response as it applies to the past 7 days. 
 
 
Not 
at all 
A little 
bit 
Som
e-
what 
Quite 
a bit 
Very 
much 
NTX
1 
I have numbness or tingling in my hands
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
2 
I have numbness or tingling in my feet
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
3 
I feel discomfort in my hands
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
4 
I feel discomfort in my feet
 ................................................................................ 
0 
1 
2 
3 
4 
 
Please circle or mark one number per line to indicate your response as it 
applies to the past 7 days. 
 
 
ADDITIONAL CONCERNS 
 
Not 
at all 
A little 
bit 
Som
e-
what 
Quite 
a bit 
Very 
much 
 
NTX
5 
I have joint pain or muscle cramps
 ................................................................................ 
0 
1 
2 
3 
4 
HI1
2 
I feel weak all over
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
6 
I have trouble hearing
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
7 
I get a ringing or buzzing in my ears
 ................................................................................ 
0 
1 
2 
3 
4 
NTX
8 
I have trouble buttoning buttons
 ................................................................................ 
0 
1 
2 
3 
4 

 
Protocol version date 03-14-23 
 
 
 
 
 
 
  
 
44  
 
NTX
9 
I have trouble feeling the shape of small objects 
when they are in my hand
 ................................................................................ 
 
0 
 
1 
 
2 
 
3 
 
4 
An6 
I have trouble walking
 ................................................................................ 
0 
1 
2 
3 
4 

A Phase II Trial Comparing Quality of Life After HIPEC in Patients with Stage IIIC and IV Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma 
Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) 
WFBCCC 83216 
 
Protocol version date 05-22-23 
 
 
 
 
 
 
 45  
 
 
Appendix K – Adverse Events Log 
WFBCCC Adverse Event (AE) Log 
PI:   
Subject PID:   
MRN:   
Cycle #:   
Cycle Start Date:   
Cycle Start 
Time:   
Cycle End Date:   
Cycle End Time:   
Adverse 
Lab 
Value 
Grade Start 
Date 
End Date Attributi 
Expect Serious 
Dose 
Action 
Therapy 
Reportable Advers Outcome 
Treating 
CTCAE Term 
(1-5) 
on DEF= ed 
Adverse 
Limitin Taken 
Given 
? IRB- IRB 
e Event R= 
MD 
per 
Definite 
N=No 
Event Detail g 
NO=None 
NO=None 
STRC- 
Report Recovered Initials/Dat 
CTC 
PROB= 
Y=Yes NO=No 
Toxitity DR=Dose 
SYM=Sympt STRC 
(AER) 
TX=Still 
e 
Probable 
LT=Life 
(DLT) 
Reduced 
omatic 
FDA- FDA 
Filed 
under 
POSS= 
Threatening 
N=No 
RI=Regime SUP= 
SPON- 
N=No 
treatment/ 
Possible 
DTH=Death 
Y=Yes 
N 
Supportive 
Sponsor 
Y=Yes 
observation 
UNLK= 
DIS=Disabilit
Interrupted 
VSUP=Vigor (Mark all 
A=Alive 
Unlikely 
y 
TD=Therap ous 
that apply) 
with 
UNRL= 
HOS=Hospit 
Y 
supportive 
sequalae 
Unrelate 
alization 
discontinue 
D=Died 
d 
CA=Caused 
D 
congenital 
INTR=Interr 
anomaly 
upted then 
RI=Required 
reduced 
intervention 
to prevent 
impairment 
Serious Adverse Event: Hospitalization; Disability; Birth Defect; Life-threatening; Death. 
CTCAE Version 5 - https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf 
STRC- Safety and Toxicity Review Committee 
Version 1/10/18