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

• ClinicalTrials.gov Identifier: NCT00769405
• Recruitment Status: Completed
• First Posted: October 9, 2008
• Last Update Posted: August 30, 2016
• Sponsor: UNICANCER
• Information provided by (Responsible Party): UNICANCER

Tracking Information

• First Submitted Date: October 8, 2008
• First Posted Date: October 9, 2008
• Last Update Posted Date: August 30, 2016
• Study Start Date: February 2008
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 29, 2016): Overall survival [ Time Frame: until 3 years ]
• Original Primary Outcome Measures (submitted: October 8, 2008): Overall survival

Current Secondary Outcome Measures (submitted: August 29, 2016)

• Recurrence-free survival [ Time Frame: until 3 years ]
• Toxicity by NCI CTCAE v.3.0 [ Time Frame: until 5 years after surgery ]
• Morbidity from surgical complications (abdominal, extra-abdominal, aplasia) [ Time Frame: until 2 months after surgery ]

Original Secondary Outcome Measures (submitted: October 8, 2008)

• Recurrence-free survival
• Toxicity by NCI CTCAE v.3.0
• Morbidity from surgical complications (abdominal, extra-abdominal, aplasia)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Systemic Chemotherapy With or Without Intraperitoneal Chemohyperthermia in Treating Patients Undergoing Surgery for Peritoneal Carcinomatosis From Colorectal Cancer
• Official Title: Phase III Study Evaluating the Use of Systemic Chemotherapy and Chemohyperthemia Intraperitoneal Preoperatively (CHIP) and After Maximum Resection of Peritoneal Carcinomatosis Originating With Colorectal Cancer

Brief Summary

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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Primary Peritoneal Cavity Cancer

Intervention

• Drug: fluorouracil
  Given IV
• Drug: leucovorin calcium
  Given IV
• Drug: oxaliplatin
  Given during surgery
• Procedure: hyperthermia treatment
  Given intraperitoneally during surgery

Study Arms

• Experimental: Arm I
  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.
  Interventions:

  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Drug: oxaliplatin
  • Procedure: hyperthermia treatment
• Experimental: 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).
  Interventions:

  • Drug: fluorouracil
  • Drug: leucovorin calcium

• Publications *: Quenet F, Elias D, Roca L, Goere D, Ghouti L, Pocard M, Facy O, Arvieux C, Lorimier G, Pezet D, Marchal F, Loi V, Meeus P, Juzyna B, de Forges H, Paineau J, Glehen O; UNICANCER-GI Group and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):256-266. doi: 10.1016/S1470-2045(20)30599-4. Epub 2021 Jan 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 8, 2008): 264
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00769405
• Other Study ID Numbers: CDR0000595024; FRE-FNCLCC-ACCORD-15/0608; EUDRACT-2006-006175-20; EU-20847
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UNICANCER
• Original Responsible Party: Not Provided
• Current Study Sponsor: UNICANCER
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Francois Quenet, MD; Institut du Cancer de Montpellier - Val d'Aurelle

• PRS Account: UNICANCER
• Verification Date: August 2016