Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)

This study has been terminated.
(drug now on market)
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00127036
First received: August 3, 2005
Last updated: November 21, 2013
Last verified: December 2011
  Purpose

The purpose of this study is to determine if the investigators can predict the sensitivity or resistance of colon cancer to the two available first line chemotherapy agents.


Condition Intervention Phase
Adenocarcinoma
Colon Cancer
Drug: XELOX
Drug: XELIRI
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants Per Treatment Arm, Per Tumor Tissue Response Classifier [ Time Frame: 30 Days After End of Treatment - Average of 6 Months ] [ Designated as safety issue: No ]
    Investigators would develop tumor tissue classifiers to predict response to the XELOX arm or XELIRI arm; with gene expression profiles on 75 patients on each of 2 arms, construct 2 classifiers to distinguish responders (complete responses, partial responses, stable disease) from non-responders (progressive disease).


Secondary Outcome Measures:
  • Number of Participants Per Treatment Arm, With Overall Survival (OS) [ Time Frame: 30 Days After End of Treatment - Average of 6 Months ] [ Designated as safety issue: No ]
    Investigators planned to evaluate the overall survival of colorectal cancer (CRC) patients treated with XELOX + bevacizumab (Arm A) or XELIRI + bevacizumab (Arm B).

  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: 30 Days After End of Treatment - Average of 6 Months ] [ Designated as safety issue: Yes ]
    Review of Serious Adverse Events (SAEs) To assess the toxicity associated with Arms A and B. Response rates and toxicity rates for each arm were to be estimated and exact (using Casella's method) 95% confidence intervals for those proportions computed. With the anticipated 75 patients in each arm, these estimated proportions would have standard errors not exceeding 7%.


Enrollment: 65
Study Start Date: October 2003
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: XELOX + Bevacizumab
Arm A: Anticipated 75 Patients - Drug: XELOX (which is Capecitabine + Oxaliplatin) by mouth + Bevacizumab intravenously as outlined in Intervention Description - To Disease Progression
Drug: XELOX
XELOX: Oxaliplatin 130 mg/m^2 intravenously (IV); Capecitabine 825 mg/m^2 by mouth (po)
Other Name: Oxaliplatin and Capecitabine
Drug: Bevacizumab
7.5 mg/kg intravenously (IV)
Other Name: Avastin®
Experimental: XELIRI + Bevacizumab
Arm B: Anticipated 75 Patients - Drug: XELIRI (which is Capecitabine + Irinotecan) by mouth + Bevacizumab intravenously as outlined in Intervention Description - To Disease Progression
Drug: XELIRI
XELIRI: Irinotecan 240 mg/m^2 IV; Capecitabine 825 mg/m^2 by mouth (po)
Other Name: Irinotecan and Capecitabine
Drug: Bevacizumab
7.5 mg/kg intravenously (IV)
Other Name: Avastin®

Detailed Description:

Colorectal cancer is the third largest cause of cancer mortality in the United States. The treatment of metastatic colorectal cancer is undergoing rapid improvement. Currently, there are two major chemotherapy regimens, which can both be combined with anti-angiogenesis treatment. These regimens are 5-Fluorouracil (5-FU) + irinotecan and 5-FU + oxaliplatin. Each therapy has roughly similar rates of response, but it is unclear which specific therapy would benefit which patients. The advent of genome wide expression analysis provides a tool to analyze these differences. In the microarray analysis of colon cancer outcome trial, sponsored by the National Institutes of Health (NIH) and Moffitt Cancer Center, patients with newly diagnosed metastatic colon cancer are biopsied and samples are preserved in ribonucleic acid (RNA) later. Patients are then randomized to either one of two state of the art regimens: capecitabine + irinotecan + avastin (bevacizumab) or capecitabine + oxaliplatin + avastin. Response to chemotherapy, time to progression, and overall survival are end points of this trial. Once accrual of patients has been met, the investigators will compare genome wide expression patterns for each group.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients with metastatic, Response Evaluation Criteria In Solid Tumors (RECIST) measurable, adenocarcinoma of the colon and/or rectum are eligible provided their disease is metastatic to the liver. The liver metastatic disease should be confirmed cytologically or histologically at the time of study biopsy or prior to the study biopsy. All pre-study scans documenting disease must be done < 4 weeks prior to registration.
  • Patients must have had no prior treatment with either irinotecan or oxaliplatin.
  • Prior adjuvant therapy with fluoropyrimidine is allowed.
  • Prior radiotherapy is allowed, but patients should have measurable disease outside the radiation port and/or progressive disease within the previously radiated volume. In addition, it must be at least 2 weeks since administration of radiation therapy and all signs of toxicity must have abated.
  • Patients must have adequate renal and hepatic function (creatinine < 1.6 and calculated creatinine clearance [Cockcroft-Gault equation] > 60 ml/min; bilirubin < 2.0; and serum glutamic oxaloacetic transaminase [SGOT] less than 3 x normal limits) obtained within 4 weeks prior to registration.
  • Alkaline phosphatase < 2.5 x upper normal limit (or < 5 x upper normal limit in the case of liver metastases or < 10 x upper normal limit in the case of bone disease)
  • Patients must have absolute neutrophil count (ANC) > 1500/mm³ and platelet count > 100,000/mm³ within 4 weeks prior to registration.
  • Have a negative serum or urine pregnancy test within 7 days prior to starting therapy (female patients of childbearing potential)

Exclusion Criteria:

  • Pregnant and breast-feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.
  • Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. Women/men of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
  • Serious, uncontrolled, concurrent infection(s). Patients must have no evidence of significant active infection (e.g., pneumonia, peritonitis, wound abscess, etc.) at time of study entry.
  • Life expectancy < 3 months
  • Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier)
  • Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Treatment for other carcinomas within the last 5 years, except cured non-melanoma skin and treated in-situ cervical cancer
  • Participation in any investigational drug study
  • Clinically significant cardiac disease of New York Heart Association Class III or greater (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
  • Evidence of central nervous system (CNS) metastases (unless CNS metastases have been stable for > 3 months) or history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
  • Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
  • Major surgery, open biopsy, or significant trauma injury within 28 days prior to Day 0
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Known, existing uncontrolled coagulopathy
  • Impaired renal function (estimated creatinine clearance < 60ml/min as calculated with Cockcroft-Gault equation
  • Unwillingness to give written informed consent
  • Unwillingness to participate or inability to comply with the protocol for the duration of the study
  • Urine protein: creatinine ratio > 1.0 at screening
  • Blood pressure of > 150/100 mmHg
  • Unstable angina
  • Clinically significant peripheral vascular disease
  • Arterial thrombotic events, stroke or transient ischemic attack (TIA) within the last 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127036

Locations
United States, Florida
North Broward Medical Center
Deerfield Beach, Florida, United States, 33064
Broward General Medical Center
Fort Lauderdale, Florida, United States, 33316
Florida Cancer Specialists
Ft. Myers, Florida, United States, 33916
Center for Cancer Care & Research - Watson Clinic
Lakeland, Florida, United States, 33805
Fawcett Memorial Hospital
Port Charlotte, Florida, United States, 33592
Martin Memorial
Stuart, Florida, United States, 34994
Tallahassee Memorial Hospital
Tallahassee, Florida, United States, 32308
Bay Area Oncology
Tampa, Florida, United States, 33607
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Space Coast Medical Associates
Titusville, Florida, United States, 32796
United States, Georgia
St. Joseph's Candler Health System
Savannah, Georgia, United States, 31405
United States, Nebraska
Southeast Nebraska Cancer Center
Lincoln, Nebraska, United States, 68510
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Roche Pharma AG
Investigators
Principal Investigator: Jonathan Strosberg, MD H. Lee Moffitt Cancer Center & Research Institute / University of South Florida
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00127036     History of Changes
Other Study ID Numbers: MCC-13449, R21 CA10135, XEL390, 2005-0729
Study First Received: August 3, 2005
Results First Received: January 5, 2012
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
colon
adenocarcinoma
adenocarcinoma-colon
adenocarcinoma-rectum

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Carcinoma
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Bevacizumab
Capecitabine
Fluorouracil
Irinotecan
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors

ClinicalTrials.gov processed this record on October 23, 2014