HOT: HIPEC in Ovarian Cancer as Initial Treatment

Phase 2

Active, not recruiting

• Conditions: Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Fallopian Tube Cancer; Ovarian Carcinoma
• Interventions: Procedure: Cytoreductive Surgery (CRS); Drug: Adjuvant Chemotherapy; Other: Questionnaire; Procedure: Hyperthermic intraperitoneal chemotherapy; Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin

• Registration Number: NCT02124421
• Lead Sponsor: Mercy Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-13
• Study First Submitted QC: 2014-04-24
• Study First Posted: 2014-04-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-19
• Primary Completion: 2027-08
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 32

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:

  1. Absolute neutrophil count (ANC) ≥1,000/mm3
  2. Platelets ≥100,000/mm3
  3. 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:

  1. Bilirubin ≤1.5 times upper limit of normal
  2. Alanine aminotransferase (ALT) ≤3 times upper limit of normal
  3. Aspartate aminotransferase (AST) ≤3 times upper limit of normal

• Blood coagulation parameters:

  1. Prothrombin time (PT) with International Normalized Ratio of ≤1.5 and a partial prothrombin time (PTT) ≤1.5 times upper limit of normal
  2. For patients on full dose warfarin, in range International Normalized Ratio (usually between 2 and 3) and
  3. Partial prothrombin time (PTT) <1.2 times upper limit of normal
  4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRS with adjuvant IV/IP chemotherapy	Questionnaire	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
CRS with adjuvant IV/IP chemotherapy	Cytoreductive Surgery (CRS)	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
CRS with adjuvant IV/IP chemotherapy	Adjuvant Chemotherapy	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
CRS with adjuvant IV/IP chemotherapy	Cisplatin	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
CRS/HIPEC with adjuvant IV chemotherapy	Cytoreductive Surgery (CRS)	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
CRS/HIPEC with adjuvant IV chemotherapy	Adjuvant Chemotherapy	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
CRS/HIPEC with adjuvant IV chemotherapy	Questionnaire	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
CRS/HIPEC with adjuvant IV chemotherapy	Hyperthermic intraperitoneal chemotherapy	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
CRS with adjuvant IV/IP chemotherapy	Paclitaxel	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
CRS/HIPEC with adjuvant IV chemotherapy	Carboplatin	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
CRS/HIPEC with adjuvant IV chemotherapy	Paclitaxel	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

Primary Outcome Measures

Name	Time	Method
Post-operative complication rates	30 days post-operative	Compare post-operative complication rates between study arms

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Mercy Medical Center; 🇺🇸 Baltimore, Maryland, United States