Debulking and Chemotherapy With or Without Intraperitoneal Chemotherapy to Treat Peritoneal Carcinomatosis

Phase 3

Completed

Conditions: Gastrointestinal Neoplasm

Interventions: Procedure: Cytoreductive surgery
Procedure: Continuous hyperthermic peritoneal perfusion (HIPEC/CHPP)

Registration Number: NCT00052962

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This study will determine which of the two following treatment regimens provides greater benefit to patients with peritoneal carcinomatosis (gastrointestinal cancer that has spread throughout the abdomen):

* Surgical removal of tumors plus heated chemotherapy during surgery, followed by one dose of chemotherapy 7 to 12 days after surgery, followed 3 weeks later by 4 months of chemotherapy; or

* Surgical removal of tumors followed by 4 months of chemotherapy, starting 1 month after surgery.

Patients 18 years of age and older with peritoneal carcinomatosis may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood tests; chest X-ray and computed tomography (CT) scans; review of pathology slides; electrocardiogram (EKG), bone scan, and brain magnetic resonance imaging (MRI), as needed; and laparotomy. Laparatomy is a surgical procedure in which an incision is made in the abdomen to look at the amount and location of tumors in the abdominal cavity. Patients whose surgery reveals that the tumors cannot be removed are taken off study. Those eligible for the study have their tumors removed during this screening laparotomy as part of the study procedure, as follows:

All participants undergo laparotomy and removal of as much tumor as possible, as described above. Patients are then randomly assigned to one of two treatment groups:

* Group 1 - During laparotomy, after tumor removal, patients receive continuous hyperthermic peritoneal perfusion (CHPP) with the anti-cancer drug cisplatin. For CHPP, the cisplatin solution is heated and delivered to the abdomen through a catheter (plastic tube), washed through the abdomen for 90 minutes, and then drained out of the body through another catheter. At the close of surgery, a small catheter, called a Tenckhoff catheter, is left in the abdomen and brought out through the skin. Between days 7 and 12 after surgery, one dose of fluorouracil and paclitaxel chemotherapy is delivered through this catheter. The catheter is removed following complete recovery from surgery and the patient is discharged from the hospital. Four to 6 weeks after the surgery, patients have CT scans of the chest, pelvis, and abdomen, and then begin intravenous (IV, through a vein) chemotherapy with oxaliplatin, 5-fluorouracil (5-FU), and leucovorin. The chemotherapy is given in 4-week courses as follows: oxaliplatin on day 1, infused over 2 hours through a vein in the arm or neck; leucovorin on days 1 and 2, infused over 2 hours, followed by 5-fluorouracil over 22 hours; leucovorin and 5-FU repeated two weeks later on days 15 and 16. This regimen is repeated two weeks later. Between each week of chemotherapy is a week break. A course of chemotherapy consists of 28 days (two weeks of chemotherapy and two 1-week breaks). Patients may receive up to four courses (total of 16 weeks) unless their disease progresses or they cannot tolerate further doses. Doses of the chemotherapy can be reduced if the side effects are too severe.

* Group 2 - Patients follow the same procedure as those in Group 1 for laparotomy, CT imaging, and IV chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. They do not receive CHPP or chemotherapy into the abdomen.

All patients undergo repeat imaging tests six weeks after surgery and at the conclusion of the intravenous (IV) chemotherapy. They return for a physical examination and CT scans every three months for the first year, every four months for the next two years, and then every six months for up to five years after treatment. They are also asked to complete quality of life questionnaires before and after surgery, at the completion of chemotherapy, and at every follow-up visit.

Detailed Description: Patients with low-grade gastrointestinal adenocarcinoma and peritoneal carcinomatosis will undergo laparotomy and tumor debulking. Patients will be randomized at completion of tumor debulking to receive continuous hyperthermic peritoneal perfusion (HIPEC,formerly CHPP) with 250 mg/m\^2 cisplatin and an intraperitoneal dwell of 5-fluorouracil 800 mg/m\^2 and paclitaxel 125 mg/m\^2 once between postoperative day 7 and 12. All patients will receive systemic oxaliplatin, leucovorin and infusional 5-FU, every other week of every four weeks starting 4 to 6 weeks after operation and continuing for four cycles. The major endpoint is time to intraperitoneal tumor progression and survival in patients stratified based on history of previous treatment with systemic chemotherapy (yes vs. no), history of prior debulking surgery; and ability to optimally vs. suboptimally debulk intraperitoneal tumor burden.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 Surgery + post op chemotherapy	Cytoreductive surgery	* Cytoreductive surgery - patients will undergo a laparotomy, surgical incision in the abdomen to assess the peritoneal cavity, with cytoreductive surgery, or tumor debulking to reduce tumor size. * Post operative chemotherapy: systemic oxaliplatin, leucovorin and infusional 5-fluorouracil (5-FU), every other week of every four weeks (two weeks per month) starting 4 to 6 weeks after operation and continuing for four cycles {16 weeks total}.
Arm 2 Surgery + HIPEC	Cytoreductive surgery	Arm 2 Surgery + Continuous hyperthermic peritoneal perfusion (CHPP/HIPEC) + post op dwell + post op chemotherapy * Cytoreductive surgery - patients will undergo a laparotomy, surgical incision in the abdomen to assess the peritoneal cavity, with cytoreductive surgery, or tumor debulking to reduce tumor size. * followed by continuous hyperthermic peritoneal perfusion (HIPEC) with 250 mg/m\^2 cisplatin * post operative dwell chemotherapy given once between post op day 7 and 12: 5-fluorouracil (5FU) 800 mg/m\^2 and paclitaxel 125 mg/m\^2 * post operative chemotherapy: systemic oxaliplatin, leucovorin and infusional 5-FU, every other week of every four weeks (two weeks per month) starting 4 to 6 weeks after operation and continuing for four cycles {16 weeks total}.
Arm 2 Surgery + HIPEC	Continuous hyperthermic peritoneal perfusion (HIPEC/CHPP)	Arm 2 Surgery + Continuous hyperthermic peritoneal perfusion (CHPP/HIPEC) + post op dwell + post op chemotherapy * Cytoreductive surgery - patients will undergo a laparotomy, surgical incision in the abdomen to assess the peritoneal cavity, with cytoreductive surgery, or tumor debulking to reduce tumor size. * followed by continuous hyperthermic peritoneal perfusion (HIPEC) with 250 mg/m\^2 cisplatin * post operative dwell chemotherapy given once between post op day 7 and 12: 5-fluorouracil (5FU) 800 mg/m\^2 and paclitaxel 125 mg/m\^2 * post operative chemotherapy: systemic oxaliplatin, leucovorin and infusional 5-FU, every other week of every four weeks (two weeks per month) starting 4 to 6 weeks after operation and continuing for four cycles {16 weeks total}.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	2003-2008	CHPP is administered as a heated cisplatin solution delivered to the abdomen through a catheter (plastic tube), washed through the abdomen for 90 minutes, and then drained out of the body through another catheter. Progression is defined as imageable tumor nodules or increasing ascites persistent on two serial computed tomography (CT) scans.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Adverse Event	2003-2008	Here is the number of participants with an adverse event. For a detailed list of adverse events see the adverse event module.