standard therapy with or without surgery and mitomycin c in treating patients with advanced limited peritoneal dissemination of colon cancer

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. heating mitomycin c to several degrees above normal body temperature and infusing it into the area around the tumor may kill more tumor cells. giving mitomycin c after surgery may kill any remaining tumor cells. it is not yet known whether standard therapy is more effective with or without surgery followed by mitomycin c. purpose: this randomized phase iii trial is studying standard therapy with or without surgery and mitomycin c in treating patients with advanced limited peritoneal dissemination of colon cancer

objectives: primary * to compare the overall survival (os) of patients with advanced limited peritoneal dissemination of colon adenocarcinoma treated with systemic therapy with vs without cytoreduction surgery and hyperthermic intraperitoneal mitomycin c. * to compare the relative os at 1 year of patients treated with these regimens. secondary * to compare the progression-free survival (pfs) of patients treated with these regimens. * to compare the relative pfs at 1 year of patients treated with these regimens. * to compare the quality of life of patients treated with these regimens. * to compare the toxicity burden of these regimens in these patients. * to compare the os and pfs according to patients' peritoneal surface tumor genotype for the nad(p)h (quinone oxidoreductase 1 \[nqo1\] 609c \>t polymorphism \[wild type vs heterozygous/homozygous mutant\]) in patients treated with these regimens. * to compare circulating tumor cells in patients treated with these regimens. outline: this is a multicenter study. patients are stratified according to presentation (synchronous vs metachronous carcinomatosis), ecog performance status (0 vs 1), disease volume (measurable vs non-measurable), prior first-line therapy for advanced disease (chemo-naïve vs prior first-line therapy), planned chemotherapy (oxaliplatin vs irinotecan vs fluorouracil/leucovorin calcium vs capecitabine), and planned biologic therapy (bevacizumab vs cetuximab vs none). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive standard systemic therapy, at the discretion of patients' oncologist, comprising combinations of fluorouracil, leucovorin calcium, irinotecan hydrochloride, oxaliplatin, and/or capecitabine (including folfox4, mfolfox6, capeox, or folfiri) with or without bevacizumab (beginning 4-6 weeks after major surgery) or cetuximab\*. treatment repeats in the absence of disease progression or unacceptable toxicity. patients with progressive disease may crossover to arm ii. note: \*for patients with kras wild-type tumors. * arm ii: patients undergo cytoreduction surgery and hyperthermic intraperitoneal mitomycin c over 45-90 minutes. beginning 8 weeks after surgery, patients receive standard systemic therapy as in arm i. treatment with systemic therapy repeats for 6 courses in the absence of disease progression or unacceptable toxicity. blood and tissue samples may be collected from patients for correlative studies. patients complete sf-36 health survey; functional assessment of cancer therapy-colorectal (fact-c); feeling sad, down, or depressed (ces-d); and a brief pain inventory quality-of-life questionnaires at baseline and then periodically during study. after completion of study therapy, patients are followed up periodically for 5 years.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed colon adenocarcinoma meeting the following criteria: * newly diagnosed disease * advanced disease * confirmed synchronous or metachronous limited peritoneal disease dissemination * no appendiceal or rectal cancer * no signet ring cell type * disease amenable to complete cytoreduction surgery as indicated by: * peritoneal cancer index (pci) ≤ 20 by helical ct scan and/or staging laparoscopy * no parenchymal hepatic metastases * no clinical (jaundice), biochemical (abnormally elevated serum bilirubin and/or alkaline phosphatase), or radiological (by ultrasound, ct scan, or mri) biliary obstruction * no symptomatic malignant ascites requiring palliative paracentesis * small volume of disease in the gastro-hepatic ligament defined by a \< 5 cm mass in the epigastric region on cross-sectional imaging * no cross-sectional imaging findings indicative of multi-segmental (\> 1 site) small bowel obstruction, small bowel loops matted together, or gross disease of the small bowel mesentery characterized by distortion, thickening, or loss of mesenteric vascular clarity * no clinical or radiological evidence of hematogenous or distant nodal (retroperitoneal, pelvic, mediastinal, peri-portal, or peri-aortic) metastasis patient characteristics: * ecog performance status 0-1 * anc \> 1,200/mm³ * wbc \> 4,000/mm³ * platelet count 150,000/mm³ * inr ≤ 1.5 * patients on therapeutic anticoagulant for unrelated medical condition such as atrial fibrillation or anti-thrombocyte treatment allowed provided treatment can be withheld for operation * total serum bilirubin ≤ 1.5 mg/dl (\> 1.5 mg/dl for patients with gilbert syndrome) * alkaline phosphatase \< 2.5 times upper limit of normal (uln) * ast \< 1.5 times uln * serum creatinine normal * bun normal * not pregnant or nursing * fertile patients must use effective contraception * no history of severe congestive heart failure or severe pulmonary disease * patients who are status post-revascularization procedures with satisfactory cardiac function are eligible * no acute myocardial infarction within the past 6 months * no significant history of a medical problem or co-morbidity (e.g., severe congestive heart failure or active ischemic heart disease) that would preclude a major abdominal operation * no concurrent second malignancy requiring systemic therapy * no psychiatric or addictive disorders, or other conditions that would preclude the patient from meeting the study requirements prior concurrent therapy: * see disease characteristics * no prior second-line systemic treatment for metastatic colon adenocarcinoma * patients who received prior adjuvant therapy for colon adenocarcinoma and/or prior first-line systemic therapy for metastatic colon adenocarcinoma are eligible

Keywords: mucinous adenocarcinoma of the colon stage iii colon cancer stage iv colon cancer