Erlotinib Hydrochloride and Irinotecan Hydrochloride in Treating Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00045201|
Recruitment Status : Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : August 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm||Drug: Erlotinib Hydrochloride Drug: Irinotecan Hydrochloride||Phase 1|
I. Determine the maximum tolerated dose (MTD) of erlotinib (erlotinib hydrochloride) and irinotecan (irinotecan hydrochloride), in relation to presence or absence of UGT1A1*28 polymorphism, in patients with advanced solid tumors that overexpress epidermal growth factor receptor.
II. Determine the dose-limiting toxicity of these regimens in these patients. III. Determine whether erlotinib alters the disposition of irinotecan using a previously described limited sampling model.
IV. Determine factors that influence the disposition of these drugs, including genetic variation in UGT1A1 and BCRP, in patients treated with these regimens.
V. Determine factors that influence the disposition of these drugs, in terms of tumor BCRP-expression, in tumor samples from patients treated with these drugs at the MTD.
VI. Evaluate the effect of this regimen on epidermal growth factor receptor phosphorylation in these patients.
VII. Assess, preliminarily, any antitumor activity in patients treated with these regimens.
VIII. Correlate, preliminarily, EGFR phosphorylation and/or BCRP -expression with response in tumor samples from these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to UGTA1A genotype (all patients regardless of genotype [closed to accrual as of 9/15/04] vs UGT1A1 6/6 genotype vs UGTA1A 6/7 or 7/7 genotype).
Patients receive oral erlotinib hydrochloride daily on days -6 to -1. Patients then receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1 and oral erlotinib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of erlotinib hydrochloride and irinotecan hydrochloride until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.
Patients are followed for 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of OSI-774 and CPT-11 in Patients With Advanced Solid Tumors|
|Actual Study Start Date :||June 13, 2002|
|Actual Primary Completion Date :||June 1, 2009|
Experimental: Treatment (enzyme inhibitor, chemotherapy)
Patients receive oral erlotinib hydrochloride daily on days -6 to -1. Patients then receive irinotecan hydrochloride IV over 90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Erlotinib Hydrochloride
Drug: Irinotecan Hydrochloride
- MTD of erlotinib hydrochloride and irinotecan hydrochloride in patients with advanced solid tumors that overexpress epidermal growth factor receptor [ Time Frame: At least 4 weeks ]Defined as the highest safely tolerated dose where at most one patient experiences DLT with the next higher dose having at least 2 patients who experience DLT. Three patients will be entered at a given dose level and observed for at least 4 weeks to assess toxicity. MTD will be determined independently for each cohort.
- Dose limiting toxicity of the combination in all cohorts [ Time Frame: At least 4 weeks ]Defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment. Graded using the National Cancer Institute Common Toxicity Criteria (CTC) version 2.0. Defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) versioun 4.0.
- Effect of erlotinib hydrochloride on the disposition of irinotecan hydrochloride [ Time Frame: Weekly during course 1 ]Analysis performed using high performance liquid chromatography assays. Serial blood samples will be obtained during Cycle 1 only to determine the pharmacokinetics of irinotecan hydrochloride and erlotinib hydrochloride.
- Effect of erlotinib on EGFR phosphorylation at MTD [ Time Frame: Weekly during course 1 ]
- Genetic variation in UGT1A1 and BCRP [ Time Frame: Weekly during course 1 ]Detected using allele-specific restriction fragment length polymorphism (RFLP) assays and GeneScan assays. The overall incidence of UTG1A1 polymorphism will be estimated and summarized.
- Tumor BCRP expression in patients treated at the MTD [ Time Frame: Weekly during course 1 ]
- Evidence of anti tumor activity [ Time Frame: Every 3 weeks ]Evaluated using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Correlation of EGFR phosphorylation and/or BCRP expression with response to this combination [ Time Frame: Every 3 weeks ]Evaluated using modified RECIST criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00045201
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Henry C Pitot||Mayo Clinic|