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

This study is ongoing, but not recruiting participants.
National Institute for Cancer Research, Italy
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
First received: August 12, 2010
Last updated: March 3, 2014
Last verified: March 2014

This study is being done to determine the maximum dose of a certain chemotherapy drug (irinotecan) that can be tolerated as part of a combination of drugs. There is a combination of chemotherapy drugs typically used to treat cancer of the colon and rectum: 5-Flurouracil (5-FU), leucovorin, and irinotecan; the combination is known as FOLFIRI. At the present time, the Food and Drug Administration (FDA) has approved this drug combination for the treatment of cancers of the colon and rectum. The FDA has also approved the use of a drug called bevacizumab (or Avastin) in combination with FOLFIRI, and this is considered one of the standards of care for all patients with colon and rectal cancer which has spread.

The best dose of irinotecan to use in the combination of FOLFIRI and bevacizumab is not known. Earlier studies have shown that higher doses of irinotecan can be used safely as part of the FOLFIRI combination, but it is unclear whether these same doses will be safe when bevacizumab is added to this combination.

Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: FOLFIRI, Avastin, Irinotecan
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Genotype-guided Phase I Study of Irinotecan Administered in Combination With 5-fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in Advanced Colorectal Cancer Patients

Resource links provided by NLM:

Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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.

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic profile of irinotecan in combination with bevacizumab. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To evaluate the effect of bevacizumab on the pharmacokinetics of irinotecan.

Estimated Enrollment: 45
Study Start Date: December 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: FOLFIRI, Avastin, Irinotecan
    Patients will be treated with the FOLFIRI regimen plus bevacizumab. Irinotecan will be administered at doses higher than the standard dose in patients with the UGT1A1*1/*1 and UGT1A1*1/*28 genotypes, while the doses of infusional 5-FU/LV and bevacizumab will remain unchanged.

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

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of metastatic colorectal adenocarcinoma
  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 toxicity.
  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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01183494

United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
CRO-National Cancer Institute
Aviano, Italy, 33081
Sponsors and Collaborators
University of Chicago
National Institute for Cancer Research, Italy
Principal Investigator: Manish Sharma, MD University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01183494     History of Changes
Other Study ID Numbers: 09-277-B
Study First Received: August 12, 2010
Last Updated: March 3, 2014
Health Authority: United States: Institutional Review Board
Italy: National Institute of Health

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015