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A Genotype-guided Phase I Study of Irinotecan Administered in Combination With 5-fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in Advanced Colorectal Cancer Patients

Phase 1
18 Years
Open (Enrolling)
Metastatic Colorectal Cancer

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Trial Information

A Genotype-guided Phase I Study of Irinotecan Administered in Combination With 5-fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in Advanced Colorectal Cancer Patients

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic colorectal

2. No prior chemotherapy for metastatic disease

3. Age ≥18 years

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (5. Life expectancy
> 3 months

5. Adequate organ function, including bone marrow (absolute neutrophil count (ANC)
≥l500/μl, haemoglobin ≥ 9g/dL, platelets ≥ 100,000/ μl); hepatic (total bilirubin <
1.6 mg/dl;SGOT and SGPT < 2.5 x upper limit of normal for patients without liver
metastases and < 5x upper limit of normal for patients with liver metastases); and
renal (serum creatinine ≤ 1.5x upper limit of normal).

6. Patients who are eligible to be registered in the study, based upon the above
criteria, will be genotyped for the UGT1A1*28 polymorphism and stratified into two
groups based on the presence of the UGT1A1*1/*1 or UGT1A1*1/*28 genotype.

7. Patients with the UGT1A1*28/*28 genotype or carriers of the other alleles (TA5 and
TA8)will be excluded.

8. For patients to be evaluable for response (a secondary end point), they must have at
least one measurable lesion as defined by RECIST (i.e., lesions that can be
accurately measured in at least one dimension with the longest diameter ≥ 20 mm using
conventional techniques or ≥ 10 mm using spiral CT scan).

9. Patients without measurable lesions can be included and will be evaluated only for

10. Signed informed consent and local IRB approval is required.

11. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation, up until 30 days after final study
treatment. Should a woman become pregnant or suspect that she is pregnant while
participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Prior irinotecan or bevacizumab treatment

2. Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

3. Diarrhea greater than grade 1

4. Bowel obstruction

5. Documented brain metastases

6. Serious active infectious disease

7. Active uncontrolled bleeding or fistulas

8. Pregnancy

9. Radiotherapy or major surgery within 4 weeks

10. Previous or concurrent malignancy, except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the
patient has been disease-free for five years.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Outcome Description:

To define the Maximum Tolerated Dose (MTD), the Dose Limiting Toxicity (DLT), and the recommended dosage of irinotecan administered in first-line therapy with FOLFIRI plus bevacizumab for patients with metastatic CRC and either the UGT1A1*1/*1 or UGT1A1*1/*28 genotype.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Manish Sharma, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago


United States: Institutional Review Board

Study ID:




Start Date:

December 2009

Completion Date:

March 2013

Related Keywords:

  • Metastatic Colorectal Cancer
  • Colorectal Neoplasms



The University of ChicagoChicago, Illinois  60637