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

Colon Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00127036
• Other study ID #: MCC-13449
• Secondary ID: R21 CA10135XEL39
• Status: Terminated
• Phase: Phase 2
• First received: August 3, 2005
• Last updated: November 21, 2013
• Start date: October 2003
• Est. completion date: December 2010

Study information

• Verified date: December 2011
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 65
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Colon Cancer

Intervention

Drug:
• XELOX
XELOX: Oxaliplatin 130 mg/m^2 intravenously (IV); Capecitabine 825 mg/m^2 by mouth (po)
• XELIRI
XELIRI: Irinotecan 240 mg/m^2 IV; Capecitabine 825 mg/m^2 by mouth (po)
• Bevacizumab
7.5 mg/kg intravenously (IV)

Locations

Country	Name	City	State
United States	North Broward Medical Center	Deerfield Beach	Florida
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Florida Cancer Specialists	Ft. Myers	Florida
United States	Center for Cancer Care & Research - Watson Clinic	Lakeland	Florida
United States	Southeast Nebraska Cancer Center	Lincoln	Nebraska
United States	Fawcett Memorial Hospital	Port Charlotte	Florida
United States	St. Joseph's Candler Health System	Savannah	Georgia
United States	Martin Memorial	Stuart	Florida
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	Bay Area Oncology	Tampa	Florida
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Space Coast Medical Associates	Titusville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Roche Pharma AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Per Treatment Arm, Per Tumor Tissue Response Classifier	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).	30 Days After End of Treatment - Average of 6 Months	No
Secondary	Number of Participants Per Treatment Arm, With Overall Survival (OS)	Investigators planned to evaluate the overall survival of colorectal cancer (CRC) patients treated with XELOX + bevacizumab (Arm A) or XELIRI + bevacizumab (Arm B).	30 Days After End of Treatment - Average of 6 Months	No
Secondary	Number of Participants With Serious Adverse Events (SAEs)	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%.	30 Days After End of Treatment - Average of 6 Months	Yes

External Links

•   H. Lee Moffitt Cancer Center & Research Institute Web Page
•   Moffitt Clinical Trials website