Protocol Number: 03-C-0085

Title:

A Prospective Random Assignment Trial for Pts With Peritoneal Carcinomatosis From Low Grade Gastrointestinal Adenocarcinoma To Treatment With Operative Debulking and Systemic Chemotherapy With or Without Intra- and Peri-Operative Intraperitoneal Chemother

Number:

03-C-0085

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 will be screened with a medical history, physical examination, and blood tests; chest x-ray and CT scans; review of pathology slides; EKG, bone scan, and brain MRI, as needed; and laparotomy. Laparotomy 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 will be taken off study. Those eligible for the study will have their tumors removed during this screening laparotomy as part of the study procedure, as follows:

All participants will undergo laparotomy and removal of as much tumor as possible, as described above. Patients will then be 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 a 4-month course of intravenous (IV, through a vein) chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. The chemotherapy is given in four 4-week cycles 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. This regimen is repeated 1 week later, followed by a 2-week break for completion of one cycle. Chemotherapy is given on an outpatient or inpatient basis, depending on the patient's comfort and side effects.

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

All patients will undergo repeat imaging tests halfway through and at the end of the IV chemotherapy. They will then return for a physical examination and CT scans every 3 months for the first year, every 4 months for the next 2 years, and then every 6 months for up to 5 years after treatment. They will also be asked to complete quality of life questionnaires before and after surgery, after every second course of IV chemotherapy, and at every follow-up visit.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

a. The patient must have histologically or cytologically proven peritoneal carcinomatosis from low-grade mucinous adenocarcinoma of the gastrointestinal tract. Patients with no tissue for examination may undergo percutaneous needle aspiration under CT or ultrasound guidance as clinically indicated or a laparotomy with biopsy if a tumor grade cannot be determined on other available material.

b. Radiologic workup must demonstrate that there is no imageable disease outside of the peritoneal cavity.

c. Radiologic workup or prior abdominal exploration must show abnormalities consistent with disease which can be debulked to a residual size of less than 1 cm in diameter per tumor deposit in the judgement of the investigators.

d. Patients must have an ECOG performance status of less than or equal to 2 on study entry and on the day prior to planned treatment.

e. Patients must have a minimum expected duration of survival of greater than 16 weeks.

f. Patients must have recovered from any severe toxicity from all prior chemotherapy, immunotherapy or radiotherapy except as outlined in appendix 1.

g. Patients must have a serum AST and ALT within 5 times the upper limit of normal and a total serum bilirubin of less than 3 times the upper limit of normal, both of which define the upper limit of grade 2 treatment related toxicities..

h. Patients must have a ANC greater than1,500/microliter.

i. Patients must be age greater than or equal to 18 years.

EXCLUSION CRITERIA:

a. Patients will be excluded if they have concomitant medical problems that would place them at unacceptable risk for a major surgical procedure.

1) Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g. age greater than 65, and a history of hypertension, first degree relative with atherosclerotic coronary artery evaluation and will not be eligible if they demonstrate significant irreversible ischemia on a stress thallium study or an ejection fraction of less than 40%.

2) Patients who have shortness of breath with minimal exertion or who are at risk for pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will not be eligible if their FEV1 is less than 1.2 liters or their maximum voluntary ventilation is less than 50% of expected.

b. Patients who have a neurological toxicity of Grade 3 or greater will be excluded because of the potential neurotoxicity associated with platinum and paclitaxel therapy.

c. Patients will be ineligible if they have a serum creatinine of greater than 1.5 mg/dL unless the measured creatinine clearance is greater than 60mL/min/1.73m(2).

d. Patients will be ineligible if platelets are less than 75, 000/mm(3).

e. Patients who have failed previous intraperitoneal chemotherapy will be ineligible.

f. Pregnant women or women who are breast-feeding will be ineligible.

g. Patients less than 30 kg will be ineligible.

h. Patients who have undergone two or more operative procedures to debulk disease, have received 2 or more regimens of systemic chemotherapy, or any previous CHPP therapy will be excluded from study.

Special Instructions: Currently Not Provided

Keywords:

Appendiceal Cancer

Regional Therapy

Carcinomatosis

Hyperthermia

Recruitment Keywords:

None

Conditions:

Gastrointestinal Neoplasm

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Bartlett DL, Buell JF, Libutti SK, Reed E, Lee KB, Figg WD, Venzon DJ, Alexander HR. A phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis. Cancer. 1998 Sep 15;83(6):1251-61. PMID: 9740093

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. PMID: 10944126

Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000 Mar 25;355(9209):1041-7. PMID: 10744089

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