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

February 22, 2024 updated by: National Cancer Institute (NCI)

Phase I Trial of OSI-774 and CPT-11 in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Active, not recruiting

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Given IV
Other Names:
  • Campto
  • Camptosar
  • U-101440E
  • CPT-11
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • Irinomedac
  • Irinotecan Hydrochloride Trihydrate
  • Irinotecan Monohydrochloride Trihydrate
Given orally
Other Names:
  • Cp-358,774
  • Tarceva
  • OSI-774
  • CP-358

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At least 4 weeks
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.
At least 4 weeks
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.
Weekly during course 1
Effect of erlotinib on EGFR phosphorylation at MTD
Time Frame: Weekly during course 1
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.
Weekly during course 1
Tumor BCRP expression in patients treated at the MTD
Time Frame: Weekly during course 1
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.
Every 3 weeks
Correlation of EGFR phosphorylation and/or BCRP expression with response to this combination
Time Frame: Every 3 weeks
Evaluated using modified RECIST criteria.
Every 3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Henry C Pitot, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2002

Primary Completion (Actual)

September 13, 2013

Study Completion (Estimated)

August 22, 2024

Study Registration Dates

First Submitted

September 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimated)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • NCI-2009-00015 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA015083 (U.S. NIH Grant/Contract)
  • U01CA069912 (U.S. NIH Grant/Contract)
  • CDR0000256910
  • 594-02 01
  • NCI-5351
  • MAYO-MC0112
  • MC0112 (Other Identifier: Mayo Clinic in Rochester)
  • 5351 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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