Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI, Other||CDR0000681540|
WRAMC-8214, USMCI-8214/ACOSOG-Z6091, 8214, NCT01167725
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
- 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.
- 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.
- Histologically or cytologically confirmed colon adenocarcinoma meeting the following criteria:
- Confirmed synchronous or metachronous limited peritoneal disease dissemination
- No appendiceal or rectal cancer
- 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
- ECOG performance status 0-1
- Platelet count 150,000/mm³
- 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)
- 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 Lead Organizations/Sponsors
Walter Reed Army Medical Center
- National Cancer Institute
Alexander Stojadinovic, Principal Investigator
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01167725
ClinicalTrials.gov processed this data on April 09, 2015
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