Hyperthermic Intraperitoneal Chemotherapy With Cisplatin During Surgery or Cisplatin Before Surgery for the Treatment of Stage III or IV Ovarian, Fallopian Tube or Peritoneal Cancer

Study Overview
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Brief Summary
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This phase I trial studies the side effects of hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery in treating patients with stage III or IV ovarian, fallopian tube or peritoneal cancer receiving chemotherapy before surgery. Hyperthermic intraepithelial chemotherapy involves the infusion of heated cytotoxic chemotherapy that circulates into the abdominal cavity at the time of surgery. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery may kill more tumor cells compared to usual care.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of intravenous (IV) cisplatin on the day prior to interval cytoreductive surgery (CRS) to administration of hyperthermic intraepithelial chemotherapy (HIPEC) with cisplatin at the completion of CRS versus standard chemotherapy and interval surgery. SECONDARY OBJECTIVES: I. Feasibility of each of the treatment options. II. Treatment delays. III. Perioperative outcomes. IV. Quality of life/patient reported outcomes. V. Recurrence free survival (RFS) and overall survival (OS). OUTLINE: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval debulking surgery Patients are randomized to 1 of 3 arms. ARM I: No chemotherapy immediately before, during or after surgery. Carboplatin/paclitaxel is given 3-4 weeks prior to surgery and again 2-4 weeks after surgery. ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of interval debulking surgery ARM III: Patients receive cisplatin IV the day prior to interval debulking surgery After completion of study treatment, patients are followed up for up to 30 days.

Official Title
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Randomized Phase I Study Assessing the Safety and Tolerability Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Completion of Interval Cytoreductive Surgery Compared to Surgery and Chemotherapy Prior to Surgery for Patients With Stage III/IV Ovarian Cancer Undergoing Neoadjuvant Chemotherapy.

Conditions
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Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Mucinous Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, Ovarian Serous Adenocarcinoma, Primary Peritoneal Endometrioid Adenocarcinoma, Primary Peritoneal Serous Adenocarcinoma, Stage III Fallopian Tube Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Primary Peritoneal Cancer AJCC v8, Stage IIIA Fallopian Tube Cancer AJCC v8, Stage IIIA Ovarian Cancer AJCC v8, Stage IIIA Primary Peritoneal Cancer AJCC v8, Stage IIIA1 Fallopian Tube Cancer AJCC v8, Stage IIIA1 Ovarian Cancer AJCC v8, Stage IIIA2 Fallopian Tube Cancer AJCC v8, Stage IIIA2 Ovarian Cancer AJCC v8, Stage IIIB Fallopian Tube Cancer AJCC v8, Stage IIIB Ovarian Cancer AJCC v8, Stage IIIB Primary Peritoneal Cancer AJCC v8, Stage IIIC Fallopian Tube Cancer AJCC v8, Stage IIIC Ovarian Cancer AJCC v8, Stage IIIC Primary Peritoneal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Primary Peritoneal Cancer AJCC v8, Stage IVA Fallopian Tube Cancer AJCC v8, Stage IVA Ovarian Cancer AJCC v8, Stage IVA Primary Peritoneal Cancer AJCC v8, Stage IVB Fallopian Tube Cancer AJCC v8, Stage IVB Ovarian Cancer AJCC v8, Stage IVB Primary Peritoneal Cancer AJCC v8

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Cisplatin
* Procedure: Cytoreductive Surgery
* Drug: Hyperthermic Intraperitoneal Chemotherapy
* Drug: Paclitaxel
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand (English-speaking), and willingness to sign a written, informed consent Age > 18 years old Newly diagnosed stage III or IV epithelial (serous, mucinous, or endometrioid) ovarian, fallopian tube or peritoneal cancer diagnosed by: Biopsy/histology (either by interventional radiology or laparoscopy) OR Cytology; If diagnosis is based on cytology the following criteria must be met: Immunohistochemistry on the block from cytology to demonstrate Mullerian origin Presence of pelvic mass AND CA 125 > 200kU/I AND CA125/CEA ratio > 25 at initial diagnosis Omental cake or other metastases larger than 2 cm in the upper abdomen and/or regional lymph node metastasis irrespective of size (diagnosed by computed tomography [CT]/magnetic resonance imaging [MRI], ultrasound, or laparoscopy) Patient planned for or currently receiving neoadjuvant chemotherapy due to the fact that optimal primary CRS was determined not to be feasible by the primary surgeon Patient must be planned or scheduled to undergo interval cytoreductive surgery after cycle 3-4 of neoadjuvant surgery Completion of three cycles of neoadjuvant chemotherapy (NACT) with standard therapy (carboplatin [area under the curve (AUC) 5-6] day [D]1 + paclitaxel [175 mg/m^2] D1 every 3 weeks) Following 3-4 cycles of NACT partial or complete response Following 3-4 cycles of NACT at least 50% decrease in CA-125 level between pre-cycle 1 and post-cycle 3/prior to surgery Fit for major surgery, American Society of Anesthesiologists (ASA )1 or ASA 2 Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-2 Serum creatinine < 1.4 mg/dL Creatinine clearance > 60 ml/min (Cockcroft-Gault formula) White blood cell count > 3.5 x 10^9 cells/L Absolute neutrophil count > 1.5 kg/ul Platelets > 100,000/ul Total bilirubin within 1.5 x normal institutional limits Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal For quality of life assessment, baseline questionnaires should be filled in before randomization Exclusion Criteria: History of breast cancer or previous malignancy within 5 years prior to inclusion, with the exception of radically excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix History or current diagnosis of inflammatory bowel disease History of allergic reactions to compounds of similar chemical or biologic composition to cisplatin, carboplatin, and paclitaxel Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia Patients in whom an optimal or complete cytoreduction cannot be performed will be excluded at the time of surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (carboplatin, paclitaxel, CRS)<br>OUTLINE: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval debulking surgery Patients are randomized to 1 of 3 arms. ARM I: No chemotherapy immediately before, during or after surgery. Carboplatin/paclitaxel is given 3-4 weeks prior to surgery and again 2-4 weeks after surgery. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Procedure: Cytoreductive Surgery<br>* Undergo CRS<br>* Other names: Cytoreduction;Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (carboplatin, paclitaxel, CRS, HIPEC, cisplatin)<br>OUTLINE: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval debulking surgery Patients are randomized to 1 of 3 arms. ARM II: Patients undergo HIPEC and receive cisplatin IV over 90 minutes at the time of interval debulking surgery | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Procedure: Cytoreductive Surgery<br>* Undergo CRS<br>* Other names: Cytoreduction;Drug: Hyperthermic Intraperitoneal Chemotherapy<br>* Undergo HIPEC<br>* Other names: HIPEC;Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm III (carboplatin, paclitaxel, CRS, cisplatin)<br>OUTLINE: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 3 weeks for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks following the third or fourth neoadjuvant cycle, patients who achieve complete or partial response undergo interval debulking surgery Patients are randomized to 1 of 3 arms. ARM III: Patients receive cisplatin IV the day prior to interval debulking surgery | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Procedure: Cytoreductive Surgery<br>* Undergo CRS<br>* Other names: Cytoreduction;Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chemotherapy-related adverse events | Defined by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. | Up to 30 days after perioperative treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of chemotherapy immediately perioperatively | Percentage of patients able to receive planned chemotherapy the day prior to surgery or HIPEC on day of surgery | 1 Day prior to surgery and 1 day of surgery | 
| Percentage of patients in Arm C with a treatment free interval of < 8 weeks | Percentage of patients in Arm C with a treatment free interval of < 8 weeks | Up to 1 year | 
| Recurrence free survival | time between surgery and recurrence | For 3-5 years after study | 
| Tumor response | tumor response evaluated per clinical standards | Up to 1 year | 
| Quality of life (QOL) assessment EORTC QLQ-C30 | Validated quality of life assessments | Baseline up to 6 months post-treatment |