A Genotype-guided Study of Irinotecan Administered in Combination With 5-fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in Advanced Colorectal Cancer Patients
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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 |
- 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.
- 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: | March 2013 |
Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
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Drug: FOLFIRI, Avastin, Irinotecan
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of metastatic colorectal adenocarcinoma
- No prior chemotherapy for metastatic disease
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (5. Life expectancy > 3 months
- 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).
- 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.
- Patients with the UGT1A1*28/*28 genotype or carriers of the other alleles (TA5 and TA8)will be excluded.
- 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).
- Patients without measurable lesions can be included and will be evaluated only for toxicity.
- Signed informed consent and local IRB approval is required.
- 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:
- Prior irinotecan or bevacizumab treatment
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Diarrhea greater than grade 1
- Bowel obstruction
- Documented brain metastases
- Serious active infectious disease
- Active uncontrolled bleeding or fistulas
- Pregnancy
- Radiotherapy or major surgery within 4 weeks
- 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.
Contact: Manish Sharma, MD | 773-834-0312 | msharma@medicine.bsd.uchicago.edu |
United States, Illinois | |
The University of Chicago | Recruiting |
Chicago, Illinois, United States, 60637 | |
Contact: Manish Sharma, MD 773-834-0312 msharma@medicine.bsd.uchicago.edu | |
Contact: , MD | |
Principal Investigator: Manish Sharma, MD | |
Italy | |
CRO-National Cancer Institute | Recruiting |
Aviano, Italy, 33081 | |
Contact: Guiseppe Toffoli, MD +39-0434-659612 gtoffoli@cro.it | |
Principal Investigator: Guiseppe Toffoli, MD |
Principal Investigator: | Manish Sharma, MD | University of Chicago |
No publications provided
Responsible Party: | Manish R. Sharma, MD, Assistant Professor of Medicine, 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: | August 29, 2012 |
Health Authority: | United States: Institutional Review Board Italy: National Institute of Health |
Additional relevant MeSH terms:
Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Fluorouracil Irinotecan Bevacizumab Leucovorin |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients Growth Substances Antineoplastic Agents, Phytogenic Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on October 17, 2012