Clinical trial NCT00127036: Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)
Official title: A Multicenter Trial for Microarray Analysis of Colon Cancer Outcome-A (MACCO-A)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma
Colon Cancer
Keywords: colon
adenocarcinoma
adenocarcinoma-colon
adenocarcinoma-rectum
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2005-08-05
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants Per Treatment Arm, Per Tumor Tissue Response Classifier
timeFrame: 30 Days After End of Treatment - Average of 6 Months
Secondary outcomes:
measure: Number of Participants Per Treatment Arm, With Overall Survival (OS)
timeFrame: 30 Days After End of Treatment - Average of 6 Months
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 30 Days After End of Treatment - Average of 6 Months
Other outcomes:
Locations:
city: Deerfield Beach
country: United States
facility: North Broward Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Ft. Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Lakeland
country: United States
facility: Center for Cancer Care & Research - Watson Clinic
state: Florida
city: Port Charlotte
country: United States
facility: Fawcett Memorial Hospital
state: Florida
city: Stuart
country: United States
facility: Martin Memorial
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Bay Area Oncology
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Titusville
country: United States
facility: Space Coast Medical Associates
state: Florida
city: Savannah
country: United States
facility: St. Joseph's Candler Health System
state: Georgia
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center
state: Nebraska
Study officials:
affiliation: H. Lee Moffitt Cancer Center & Research Institute / University of South Florida
name: Jonathan Strosberg, MD
role: PRINCIPAL_INVESTIGATOR
References: