Back to resultsStandard Therapy With or Without Surgery and Mitomycin C in Treating Patients With Advanced Limited Peritoneal Dissemination of Colon Cancer
Primary Purpose
Colorectal Cancer
Status
Unknown status
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
cetuximab
FOLFIRI regimen
FOLFOX regimen
capecitabine
fluorouracil
irinotecan hydrochloride
leucovorin calcium
mitomycin C
oxaliplatin
therapeutic conventional surgery
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring mucinous adenocarcinoma of the colon, stage III colon cancer, stage IV colon cancer
Eligibility 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
Sites / Locations
- St. Agnes Hospital Cancer Center
- Wake Forest University Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm I
Arm II
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Overall survival (OS)
Secondary Outcome Measures
Progression-free survival (PFS)
Quality of life
Toxicity burden
Circulating tumor cells
Comparison of OS and PFS according to patients' peritoneal surface tumor genotype for the NAD(P)H
Full Information
NCT ID
NCT01167725
First Posted
July 21, 2010
Last Updated
January 21, 2012
Sponsor
Walter Reed Army Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01167725
Brief Title
Standard Therapy With or Without Surgery and Mitomycin C in Treating Patients With Advanced Limited Peritoneal Dissemination of Colon Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Unknown status
Study Start Date
August 2010 (undefined)
Primary Completion Date
May 2014 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Walter Reed Army Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
mucinous adenocarcinoma of the colon, stage III colon cancer, stage IV colon cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Masking
None (Open Label)
Allocation
Randomized
Enrollment
340 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
cetuximab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
FOLFIRI regimen
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
FOLFOX regimen
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
mitomycin C
Intervention Description
Given intraperitoneally
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Patients undergo cytoreductive surgery
Primary Outcome Measure Information:
Title
Overall survival (OS)
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Title
Quality of life
Title
Toxicity burden
Title
Circulating tumor cells
Title
Comparison of OS and PFS according to patients' peritoneal surface tumor genotype for the NAD(P)H
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Stojadinovic, MD
Organizational Affiliation
Walter Reed Army Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Agnes Hospital Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Wake Forest University Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1096
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Standard Therapy With or Without Surgery and Mitomycin C in Treating Patients With Advanced Limited Peritoneal Dissemination of Colon Cancer
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