Standard Therapy With or Without Surgery and Mitomycin C in Treating Patients With Advanced Limited Peritoneal Dissemination of Colon Cancer

NCT ID: NCT01167725

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2012-01-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Colorectal Cancer

Keywords

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mucinous adenocarcinoma of the colon stage III colon cancer stage IV colon cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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), bevacizumab, or cetuximab. Treatment repeats in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may crossover to arm II.

Group Type ACTIVE_COMPARATOR

bevacizumab

Intervention Type BIOLOGICAL

Given IV

cetuximab

Intervention Type BIOLOGICAL

Given IV

FOLFIRI regimen

Intervention Type DRUG

Given IV

FOLFOX regimen

Intervention Type DRUG

Given IV

capecitabine

Intervention Type DRUG

Given IV

fluorouracil

Intervention Type DRUG

Given IV

irinotecan hydrochloride

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

Given IV

oxaliplatin

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

Given IV

cetuximab

Intervention Type BIOLOGICAL

Given IV

FOLFIRI regimen

Intervention Type DRUG

Given IV

FOLFOX regimen

Intervention Type DRUG

Given IV

capecitabine

Intervention Type DRUG

Given IV

fluorouracil

Intervention Type DRUG

Given IV

irinotecan hydrochloride

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

Given IV

mitomycin C

Intervention Type DRUG

Given intraperitoneally

oxaliplatin

Intervention Type DRUG

Given IV

therapeutic conventional surgery

Intervention Type PROCEDURE

Patients undergo cytoreductive surgery

Interventions

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bevacizumab

Given IV

Intervention Type BIOLOGICAL

cetuximab

Given IV

Intervention Type BIOLOGICAL

FOLFIRI regimen

Given IV

Intervention Type DRUG

FOLFOX regimen

Given IV

Intervention Type DRUG

capecitabine

Given IV

Intervention Type DRUG

fluorouracil

Given IV

Intervention Type DRUG

irinotecan hydrochloride

Given IV

Intervention Type DRUG

leucovorin calcium

Given IV

Intervention Type DRUG

mitomycin C

Given intraperitoneally

Intervention Type DRUG

oxaliplatin

Given IV

Intervention Type DRUG

therapeutic conventional surgery

Patients undergo cytoreductive surgery

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexander Stojadinovic, MD

Role: PRINCIPAL_INVESTIGATOR

Walter Reed Army Medical Center

Locations

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St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Countries

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United States

Other Identifiers

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WRAMC-8214, Z6091

Identifier Type: -

Identifier Source: secondary_id

CDR0000681540

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-01572

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000681540

Identifier Type: -

Identifier Source: org_study_id