Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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

Further Study Information

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Walter Reed Army Medical Center

Alexander Stojadinovic

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01167725
Information obtained from ClinicalTrials.gov on April 04, 2013

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