Pilot / Phase III Randomized Trial Comparing Standard Systemic Therapy to Cytoreduction + Hyperthermic Intraperitoneal Mitomycin C + Standard Systemic Therapy in Patients With Limited Peritoneal Dissemination of Colon Adenocarcinoma
- 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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Overall survival (OS)
Alexander Stojadinovic, MD
Walter Reed Army Medical Center
United States: Federal Government
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|St. Agnes Hospital Cancer Center||Baltimore, Maryland 21229|