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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01167725
First received: July 21, 2010
Last updated: January 21, 2012
Last verified: January 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Colorectal Cancer
 Biological: bevacizumab
Biological: cetuximab
Drug: FOLFIRI regimen
Drug: FOLFOX regimen
Drug: capecitabine
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: mitomycin C
Drug: oxaliplatin
Procedure: therapeutic conventional surgery
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival (OS) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Toxicity burden [ Designated as safety issue: Yes ]
  • Circulating tumor cells [ Designated as safety issue: No ]
  • Comparison of OS and PFS according to patients' peritoneal surface tumor genotype for the NAD(P)H [ Designated as safety issue: No ]

Estimated Enrollment: 340
Study Start Date: August 2010
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
 Biological: bevacizumab
Given IV
Biological: cetuximab
Given IV
Drug: FOLFIRI regimen
Given IV
Drug: FOLFOX regimen
Given IV
Drug: capecitabine
Given IV
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: 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.
 Biological: bevacizumab
Given IV
Biological: cetuximab
Given IV
Drug: FOLFIRI regimen
Given IV
Drug: FOLFOX regimen
Given IV
Drug: capecitabine
Given IV
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV
Drug: mitomycin C
Given intraperitoneally
Drug: oxaliplatin
Given IV
Procedure: therapeutic conventional surgery
Patients undergo cytoreductive surgery

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01167725

Locations
United States, Maryland
St. Agnes Hospital Cancer Center
Baltimore, Maryland, United States, 21229
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Walter Reed Army Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Alexander Stojadinovic, MD Walter Reed Army Medical Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Alexander Stojadinovic, Walter Reed Army Medical Center
ClinicalTrials.gov Identifier: NCT01167725     History of Changes
Other Study ID Numbers: CDR0000681540, WRAMC-8214
Study First Received: July 21, 2010
Last Updated: January 21, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
mucinous adenocarcinoma of the colon
stage III colon cancer
stage IV colon cancer

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
 Rectal Diseases
Mitomycins
Mitomycin
Oxaliplatin
Irinotecan
Capecitabine
Bevacizumab
Cetuximab
Fluorouracil
Camptothecin
Leucovorin
Levoleucovorin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013