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

Phase 2
18 Years
Not Enrolling
Adenocarcinoma, Colon Cancer

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Trial Information

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

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.

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

- 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

- 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

- 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

- Lack of physical integrity of the upper gastrointestinal tract or malabsorption

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants Per Treatment Arm, Per Tumor Tissue Response Classifier

Outcome Description:

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).

Outcome Time Frame:

30 Days After End of Treatment - Average of 6 Months

Safety Issue:


Principal Investigator

Jonathan Strosberg, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center & Research Institute / University of South Florida


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

December 2010

Related Keywords:

  • Adenocarcinoma
  • Colon Cancer
  • colon
  • adenocarcinoma
  • adenocarcinoma-colon
  • adenocarcinoma-rectum
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms



Broward General Medical Center Fort Lauderdale, Florida  33316
Tallahassee Memorial Hospital Tallahassee, Florida  32308
Florida Cancer Specialists Fort Myers, Florida  33901
H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida  33612
Bay Area Oncology Tampa, Florida  33607
Fawcett Memorial Hospital Port Charlotte, Florida  33952
North Broward Medical Center Dearfield Beach, Florida  33064-3596
Space Coast Medical Associates Cocoa Beach, Florida  32931
Southeast Nebraska Cancer Center Lincoln, Nebraska  68510
Center for Cancer Care & Research - Watson Clinic Lakeland, Florida  33805
Martin Memorial Stuart, Florida  34994
St. Joseph's Candler Health System Savannah, Georgia  31405