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

NCT00045201 | Active Not Recruiting Phase 1

• 9 other identifiers: NCI-2009-00015CDR0000256910594-02 01NCI-5351MAYO-MC0112MC01125351P30CA015083U01CA069912
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• Effect of erlotinib on EGFR phosphorylation at MTD

  Weekly during course 1

• 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

• Tumor BCRP expression in patients treated at the MTD

  Weekly during course 1

• Evidence of anti tumor activity

  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

  Evaluated using modified RECIST criteria.

  Every 3 weeks

Study Arms (1)

Treatment (enzyme inhibitor, chemotherapy)

EXPERIMENTAL

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

Interventions

Erlotinib Hydrochloride DRUG

Given orally

Also known as: CP 358, CP-358, Cp-358,774, CP358, OSI 774, OSI-774, OSI774, Tarceva

Treatment (enzyme inhibitor, chemotherapy)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, CPT11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U 101440E, U-101440E, U101440E

Treatment (enzyme inhibitor, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Erlotinib Hydrochloride; Irinotecan

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Henry C Pitot

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2002
• First Posted: January 27, 2003
• Study Start: June 13, 2002
• Primary Completion: September 13, 2013
• Study Completion (Estimated): August 22, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-02

Locations

US (1)