HOT: HIPEC in Ovarian Cancer as Initial Treatment

NCT ID: NCT02124421

Last Updated: 2024-11-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2028-04-30

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.

Conditions

Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Ovarian Carcinoma; Fallopian Tube Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CRS with adjuvant IV/IP 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

Group Type: ACTIVE_COMPARATOR

Cytoreductive Surgery (CRS)

Intervention Type: PROCEDURE

Cytoreductive surgery

Adjuvant Chemotherapy

Intervention Type: DRUG

Six weeks post-surgery (CRS or CRS/HIPEC) standard combination chemotherapy will be administered every 21 days for 6 cycles

Questionnaire

Intervention Type: OTHER

Questionnaires designed to assess quality of life in ovarian cancer patients will be administered to study participants

Paclitaxel

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Day 2: cisplatin 75 mg/m2 IP (intraperitoneal). Repeat every 21 days for 6 cycles

CRS/HIPEC with adjuvant IV 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

Group Type: EXPERIMENTAL

Cytoreductive Surgery (CRS)

Intervention Type: PROCEDURE

Cytoreductive surgery

Adjuvant Chemotherapy

Intervention Type: DRUG

Six weeks post-surgery (CRS or CRS/HIPEC) standard combination chemotherapy will be administered every 21 days for 6 cycles

Questionnaire

Intervention Type: OTHER

Questionnaires designed to assess quality of life in ovarian cancer patients will be administered to study participants

Hyperthermic intraperitoneal chemotherapy

Intervention Type: PROCEDURE

Hyperthermic intraperitoneal chemotherapy with carboplatin, AUC=6

Carboplatin

Intervention Type: DRUG

AUC=6 mg/mL/min IV (in the vein), on day 1. Repeat every 21 days for 6 cycles.

Paclitaxel

Intervention Type: DRUG

175 mg/m2 IV (in the vein), day 1. Repeat every 21 days for 6 cycles

Interventions

Cytoreductive Surgery (CRS)

Cytoreductive surgery

Intervention Type: PROCEDURE

Adjuvant Chemotherapy

Six weeks post-surgery (CRS or CRS/HIPEC) standard combination chemotherapy will be administered every 21 days for 6 cycles

Intervention Type: DRUG

Questionnaire

Questionnaires designed to assess quality of life in ovarian cancer patients will be administered to study participants

Intervention Type: OTHER

Hyperthermic intraperitoneal chemotherapy

Hyperthermic intraperitoneal chemotherapy with carboplatin, AUC=6

Intervention Type: PROCEDURE

Carboplatin

AUC=6 mg/mL/min IV (in the vein), on day 1. Repeat every 21 days for 6 cycles.

Intervention Type: DRUG

Paclitaxel

175 mg/m2 IV (in the vein), day 1. Repeat every 21 days for 6 cycles

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Cisplatin

Day 2: cisplatin 75 mg/m2 IP (intraperitoneal). Repeat every 21 days for 6 cycles

Intervention Type: DRUG

Other Intervention Names

CRS; Post-operative chemotherapy; Systemic chemotherapy; FACT-O Questionnaire; HIPEC; Paraplatin; Taxol; Taxol; CDDP

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mercy Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teresa Diaz-Montes, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mercy Medical Center

Armando Sardi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mercy Medical Center

Locations

Mercy Medical Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

MMC-2014-17

Identifier Type: -

Identifier Source: org_study_id