HOT: HIPEC in Ovarian Cancer as Initial Treatment

Study Overview
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Brief Summary
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Community hospital based phase II (prospective randomized) study to evaluate the toxicity of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in newly diagnosed, otherwise untreated, advanced stage (stage III/IV) epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Detailed Description
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Primary endpoints: To assess the feasibility of recruitment Compare complication rates between the two study arms: CRS with HIPEC and CRS alone. Secondary endpoints: To determine risk factors for morbidity and mortality Assess completion rate of 6 cycles of systemic chemotherapy To determine progression free survival at 24 months To determine overall survival at 1, 3, and 5 years Evaluate health related quality of life Patients who meet study criteria will be randomized into one of two treatment arms: 1) cytoreductive surgery (CRS) with carboplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) followed by IV combination chemotherapy with carboplatin and paclitaxel or 2) cytoreductive surgery (CRS) alone followed by adjuvant intraperitoneal (IP) and IV chemotherapy with combination cisplatin and paclitaxel for newly diagnosed advanced stage (stage III/IV) ovarian, fallopian tube or primary peritoneal cancer. Both study arms will receive 6 cycles of adjuvant chemotherapy. Twenty-four patients will undergo CRS with HIPEC performed by surgical and gynecologic oncologic surgeons at Mercy Medical Center, followed by systemic IV chemotherapy with carboplatin (AUC=6) and paclitaxel (175mg/m2) for 6 cycles postoperatively. Twenty-four patients will undergo CRS only performed by surgical and gynecologic oncologic surgeons at Mercy Medical Center, followed by IV/IP chemotherapy with Day 1: IV paclitaxel (135 mg/m2), Day 2: IP cisplatin (75 mg/m2), and Day 8: IP paclitaxel (60 mg/m2) for 6 cycles postoperatively.

Official Title
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Phase II Randomized Study: Cytoreductive Surgery (CRS) With/Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Adjuvant Chemotherapy as Initial Treatment of Ovarian, Fallopian Tube, & Primary Peritoneal Cancer

Conditions
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Epithelial Ovarian Cancer, Stage III Ovarian Cancer, Stage IV Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma, Ovarian Carcinoma, Fallopian Tube Carcinoma

Intervention / Treatment
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* Procedure: Cytoreductive Surgery (CRS)
* Drug: Adjuvant Chemotherapy
* Other: Questionnaire
* Procedure: Hyperthermic intraperitoneal chemotherapy
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Paclitaxel
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical presentation of ovarian, fallopian tube or primary peritoneal cancer Stage III/IV disease No prior treatment or significant surgery for the management of ovarian, fallopian tube, or primary peritoneal carcinoma; History of laparoscopic procedures to obtain diagnostic biopsies will be permitted in the study Histological confirmation Eastern Cooperative Oncology Group performance status 0-2 or Karnofsky performance status ≥ 70% ≤1 cm residual disease at the completion of the cytoreductive surgery (GOG criteria for optimally cytoreduction) Bone marrow function: Absolute neutrophil count (ANC) ≥1,000/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥ 8.5 g/dL Renal function: 1) Creatinine ≤1.5 times the upper limit of normal or a calculated creatinine clearance ≥60ml/min Hepatic function: Bilirubin ≤1.5 times upper limit of normal Alanine aminotransferase (ALT) ≤3 times upper limit of normal Aspartate aminotransferase (AST) ≤3 times upper limit of normal Blood coagulation parameters: Prothrombin time (PT) with International Normalized Ratio of ≤1.5 and a partial prothrombin time (PTT) ≤1.5 times upper limit of normal For patients on full dose warfarin, in range International Normalized Ratio (usually between 2 and 3) and Partial prothrombin time (PTT) <1.2 times upper limit of normal Candidate for administration of postoperative standard platinum-based combination systemic chemotherapy (adequate bone marrow, renal, hepatic function, and blood coagulation parameters) Exclusion Criteria: Any prior treatment modality for the diagnosis of ovarian, fallopian tube, or primary peritoneal cancerPrior surgical attempt of cytoreductive surgery Stage I/II disease Presence of other invasive malignancies or evidence of other cancer within the past 3 years Known active acute hepatitis and confirmed diagnosis of HIV Active systemic infection that requires use of parenteral antibiotics History of acute coronary syndromes (ACS), within the last 6 months, according to AHA definitions New York Heart Association (NYHA) Class II or higher congestive heart failure according to American Heart Association (AHA) definitions Canadian Cardiovascular Society (CCS) Class II or higher angina grade according to AHA definitions Uncontrolled hypertension defined as > 140/90 and not cleared for surgery at time of consent by cardiologist History of cerebral artery disease and prior stroke according to AHA definitions in the last 6 months Renal insufficiency with serum creatinine level ≥1.5 times the upper limit of normal or calculated creatinine clearance <60 ml/min Patients with concurrent severe medical problems unrelated to malignancy that will preclude compliance with the study or places at an unacceptable risk for participation in the study determinate by study investigators Pregnant women are excluded from this study because carboplatin is category D agent with the potential of teratogenic effects. Due to potential risk for adverse events in nursing infants secondary to treatment of the mother with carboplatin, breastfeeding should be discontinued Life expectancy of < 12 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

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: CRS with adjuvant IV/IP chemotherapy<br>Patients undergo cytoreductive surgery (CRS) alone with IV/IP combination adjuvant chemotherapy. Day 1: IV paclitaxel (135 mg/m2), day 2: IP cisplatin (75 mg/m2), and day 8: IP paclitaxel (60 mg/m2) given every 21 days for a total of 6 cycles. Standard of care treatment. Administration of quality of life questionnaires throughout study duration of follow-up | Procedure: Cytoreductive Surgery (CRS)<br>* Cytoreductive surgery<br>* Other names: CRS;Drug: Adjuvant Chemotherapy<br>* Six weeks post-surgery (CRS or CRS/HIPEC) standard combination chemotherapy will be administered every 21 days for 6 cycles<br>* Other names: Systemic chemotherapy;Other: Questionnaire<br>* Questionnaires designed to assess quality of life in ovarian cancer patients will be administered to study participants<br>* Other names: FACT-O Questionnaire;Drug: Paclitaxel<br>* Day 1: paclitaxel 135 mg/m2 IV (in the vein). Repeat every 21 days for 6 cycles Day 8: paclitaxel 60 mg/m2 IP (intraperitoneal). Repeat every 21 days for 6 cycles<br>* Other names: Taxol;Drug: Cisplatin<br>* Day 2: cisplatin 75 mg/m2 IP (intraperitoneal). Repeat every 21 days for 6 cycles<br>* Other names: CDDP;|
| Experimental: CRS/HIPEC with adjuvant IV chemotherapy<br>Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) administered using carboplatin for 90 minutes. Adjuvant systemic IV combination chemotherapy with carboplatin and paclitaxel (Carboplatin AUC 6, Paclitaxel 175mg/m2) will be given every 21 days for a total of 6 cycles. Administration of quality of life questionnaires throughout study duration of follow-up | Procedure: Cytoreductive Surgery (CRS)<br>* Cytoreductive surgery<br>* Other names: CRS;Drug: Adjuvant Chemotherapy<br>* Six weeks post-surgery (CRS or CRS/HIPEC) standard combination chemotherapy will be administered every 21 days for 6 cycles<br>* Other names: Systemic chemotherapy;Other: Questionnaire<br>* Questionnaires designed to assess quality of life in ovarian cancer patients will be administered to study participants<br>* Other names: FACT-O Questionnaire;Procedure: Hyperthermic intraperitoneal chemotherapy<br>* Hyperthermic intraperitoneal chemotherapy with carboplatin, AUC=6<br>* Other names: HIPEC;Drug: Carboplatin<br>* AUC=6 mg/mL/min IV (in the vein), on day 1. Repeat every 21 days for 6 cycles.<br>* Other names: Paraplatin;Drug: Paclitaxel<br>* 175 mg/m2 IV (in the vein), day 1. Repeat every 21 days for 6 cycles<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative complication rates | Compare post-operative complication rates between study arms | 30 days post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of quality of life | FACT-O questionnaire to assess quality of life in both study arms | Baseline, 4 weeks post-operative, upon completion of systemic chemotherapy, and years 1, 2, 3, 4, & 5 | 
| Evaluate the rate of progression free survival | Time from intervention to disease recurrence | at 24 months | 
| Evaluate overall survival | Time from intervention to death | at 1, 3, and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, Cytoreductive surgery, Hyperthermic Intraperitoneal chemotherapy, Systemic chemotherapy, Primary peritoneal carcinoma, Fallopian Tube cancer, Intraperitoneal chemotherapy, IV/IP chemotherapy, IV chemotherapy