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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00045201
Other study ID # NCI-2009-00015
Secondary ID NCI-2009-00015CD
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date June 13, 2002
Est. completion date August 22, 2024

Study information

Verified date February 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Phase I trial to study the effectiveness of combining erlotinib hydrochloride with irinotecan hydrochloride in treating patients who have advanced solid tumors. Erlotinib hydrochloride may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib hydrochloride and chemotherapy may kill more tumor cells.


Description:

OBJECTIVES: 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.


Other known NCT identifiers
  • NCT01646892
  • NCT01664286

Recruitment information / eligibility

Status Active, not recruiting
Enrollment 60
Est. completion date August 22, 2024
Est. primary completion date September 13, 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologically confirmed malignancy that overexpresses epidermal growth factor receptor (EGFR) - Unresectable disease for which there is no known standard therapy that ispotentially curative or definitely capable of extending life expectancy - UGT1A1 genotype 6/6, 6/7, or 7/7 - Willing to provide biologic specimens - Lesions amenable for 2 biopsies from the same tumor site (only patients receiving MTD in groups 2 and 3) - No known brain metastases - Performance status - ECOG 0-2 - At least 12 weeks - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - Hemoglobin at least 9.0 g/dL - Bilirubin no greater than 1.5 times upper limit of normal (ULN) - AST = 2.5 times ULN (5 times ULN if liver metastases present) - Creatinine no greater than 1.5 times ULN - No symptomatic congestive heart failure - No unstable angina pectoris - No cardiac arrhythmia - No New York Heart Association class III or IV heart disease - No gastrointestinal tract disease resulting in an inability to take oral or nasogastric medication - No requirement for IV alimentation - No active peptic ulcer disease - No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome) - No congenital abnormality (e.g., Fuch's dystrophy) - No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) - No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test) - No other uncontrolled concurrent illness - No ongoing or active infection - No significant traumatic injury within the past 21 days - No seizure disorder - No psychiatric illness or social situation that would preclude study compliance - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No concurrent grapefruit or grapefruit juice - No smoking during study - More than 4 weeks since prior immunotherapy or biologic therapy - No concurrent immunotherapy - More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered - No other concurrent chemotherapy - Not specified - More than 4 weeks since prior radiotherapy - No prior radiotherapy to more than 25% of bone marrow - No concurrent radiotherapy - More than 3 weeks since prior major surgery - No prior surgical procedures affecting absorption - No prior EGFR-targeting therapy (e.g., gefitinib or EKB-569) - No other concurrent investigational therapy - No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine, or valproic acid) - No concurrent combination antiretroviral therapy for HIV-positive patients - No concurrent enrollment on another study involving pharmacological agents for symptom control or therapeutic intent

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Erlotinib Hydrochloride
Given orally
Irinotecan Hydrochloride
Given IV

Locations

Country Name City State
United States Mayo Clinic in Rochester Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary MTD of erlotinib hydrochloride and irinotecan hydrochloride in patients with advanced solid tumors that overexpress epidermal growth factor receptor 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. At least 4 weeks
Primary Dose limiting toxicity of the combination in all cohorts 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. At least 4 weeks
Primary Effect of erlotinib hydrochloride on the disposition of irinotecan hydrochloride 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. Weekly during course 1
Primary Effect of erlotinib on EGFR phosphorylation at MTD Weekly during course 1
Primary Genetic variation in UGT1A1 and BCRP Detected using allele-specific restriction fragment length polymorphism (RFLP) assays and GeneScan assays. The overall incidence of UTG1A1 polymorphism will be estimated and summarized. Weekly during course 1
Primary Tumor BCRP expression in patients treated at the MTD Weekly during course 1
Primary Evidence of anti tumor activity Evaluated using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Every 3 weeks
Primary Correlation of EGFR phosphorylation and/or BCRP expression with response to this combination Evaluated using modified RECIST criteria. Every 3 weeks
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