Erlotinib Hydrochloride and Irinotecan Hydrochloride in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00045201

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-13
• Study Completion Date: 2026-08-22

Brief 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.

Detailed 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.

Conditions

Adult Solid Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Erlotinib Hydrochloride

Intervention Type: DRUG

Given orally

Irinotecan Hydrochloride

Intervention Type: DRUG

Given IV

Interventions

Erlotinib Hydrochloride

Given orally

Intervention Type: DRUG

Irinotecan Hydrochloride

Given IV

Intervention Type: DRUG

Other Intervention Names

CP 358; CP-358; Cp-358,774; CP358; OSI 774; OSI-774; OSI774; Tarceva; Campto; Camptosar; Camptothecin 11; Camptothecin-11; CPT 11; CPT-11; CPT11; Irinomedac; Irinotecan Hydrochloride Trihydrate; Irinotecan Monohydrochloride Trihydrate; U 101440E; U-101440E; U101440E

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henry C Pitot

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

NCI-2009-00015

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000256910

Identifier Type: -

Identifier Source: secondary_id

594-02 01

Identifier Type: -

Identifier Source: secondary_id

NCI-5351

Identifier Type: -

Identifier Source: secondary_id

MAYO-MC0112

Identifier Type: -

Identifier Source: secondary_id

MC0112

Identifier Type: OTHER

Identifier Source: secondary_id

5351

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00015

Identifier Type: -

Identifier Source: org_study_id

NCT01646892

Identifier Type: -

Identifier Source: nct_alias

NCT01664286

Identifier Type: -

Identifier Source: nct_alias