Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer

Unicancer

Status and phase: Completed; Phase 3

Conditions: Primary Peritoneal Cavity Cancer; Colorectal Cancer

Treatments: Procedure: hyperthermia treatment; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT00769405

FRE-FNCLCC-ACCORD-15/0608

CDR0000595024

EUDRACT-2006-006175-20

EU-20847

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether systemic chemotherapy is more effective with or without intraperitoneal chemohyperthermia in treating patients with peritoneal carcinomatosis from colorectal cancer.

PURPOSE: This randomized phase III trial is studying systemic chemotherapy to see how well it works compared with or without intraperitoneal chemohyperthermia in treating patients undergoing surgery for peritoneal carcinomatosis from colorectal cancer.

Full description

OBJECTIVES:

Primary

• Compare overall survival of patients with peritoneal carcinoma of colorectal origin undergoing complete surgical resection and receiving systemic chemotherapy with versus without intraperitoneal chemohyperthermia.

Secondary

• Evaluate recurrence-free survival of these patients.
• Evaluate treatment toxicities.
• Determine morbidity from surgical complications.
• Determine prognostic factors of survival.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, residual tumor status (R0/R1 vs R2 ≤ 1 mm), prior regimens of systemic chemotherapy (first vs ≥ second), and preoperative systemic chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

All patients undergo maximal surgical resection of the tumor.

• Arm I: Patients receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and/or after surgery). Patients must stop systemic chemotherapy at least 1 month before receiving intraperitoneal chemohyperthermia (CHIP). If bevacizumab is given as neoadjuvant therapy, then systemic chemotherapy must be discontinued 6 weeks before beginning CHIP. Patients undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes.
• Arm II: Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery).

Tumor markers (ACE and CA 19-9) are assessed at baseline, at 1 month after surgery, and then at follow-up visits.

After completion of study therapy, patients are followed at 1 and 3 months, every 3 months for 3 years, and then every 6 months for 2 years.

Enrollment: 264 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

  • Peritoneal carcinoma extension ≤ 25 (Sugarbaker Index) (determined intraoperatively)

    • Planning to receive standard systemic chemotherapy

      • Chemotherapy for metastatic cancer should be initiated 3 months after surgery

    • No extraperitoneal metastases, including liver and lung metastasis

    • No carcinomatosis of other origin besides colorectal, in particular appendical carcinomatosis

• Macroscopically complete resection (R1) or surgical reduction of tumor to a residual thickness ≤ 1 mm (R2) is possible

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• Creatinine ≤ 1.25 times ULN
• Eligible for surgery
• No peripheral neuropathy > grade 3
• Not pregnant or nursing
• No other cancer in the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
• No inability to submit to follow-up medical testing for geographical, social, or psychological reasons
• Affiliated with a social security program
• Not deprived of liberty or under supervision

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemohyperthermia
• No concurrent participation in another study of first-line therapy for this cancer

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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264 participants in 2 patient groups

Arm I

Experimental group

Description:

Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery). Patients also undergo CHIP comprising oxaliplatin intraperitoneally during surgery and hyperthermia for 30 minutes.

Treatment:

Drug: oxaliplatin

Drug: leucovorin calcium

Drug: fluorouracil

Procedure: hyperthermia treatment

Arm II

Experimental group

Description:

Patients undergo surgery and receive standard systemic chemotherapy comprising leucovorin calcium IV followed by fluorouracil IV over 30 minutes. Systemic chemotherapy will continue for at least 6 months (before and after surgery).

Treatment:

Drug: leucovorin calcium

Drug: fluorouracil