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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01167725
• Other study ID #: CDR0000681540
• Secondary ID: WRAMC-8214
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 21, 2010
• Last updated: January 21, 2012
• Start date: August 2010

Study information

• Verified date: January 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 340
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Biological:
• bevacizumab
Given IV
• cetuximab
Given IV

Drug:
• FOLFIRI regimen
Given IV
• FOLFOX regimen
Given IV
• capecitabine
Given IV
• fluorouracil
Given IV
• irinotecan hydrochloride
Given IV
• leucovorin calcium
Given IV
• mitomycin C
Given intraperitoneally
• oxaliplatin
Given IV

Procedure:
• therapeutic conventional surgery
Patients undergo cytoreductive surgery

Locations

Country	Name	City	State
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Walter Reed Army Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)			No
Secondary	Progression-free survival (PFS)			No
Secondary	Quality of life			No
Secondary	Toxicity burden			Yes
Secondary	Circulating tumor cells			No
Secondary	Comparison of OS and PFS according to patients' peritoneal surface tumor genotype for the NAD(P)H			No