Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: September 6, 2002
Last updated: May 23, 2017
Last verified: November 2016
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.

Condition Intervention Phase
Adult Solid Neoplasm
Drug: Erlotinib Hydrochloride
Drug: Irinotecan Hydrochloride
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase I Trial of OSI-774 and CPT-11 in Patients With Advanced Solid Tumors

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Correlation of EGFR phosphorylation and/or BCRP expression with response to this combination [ Time Frame: Every 3 weeks ]
    Evaluated using modified RECIST criteria.

  • 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 ]
  • Evidence of anti tumor activity [ Time Frame: Every 3 weeks ]
    Evaluated using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

  • 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.

  • 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.

  • Tumor BCRP expression in patients treated at the MTD [ Time Frame: Weekly during course 1 ]

Enrollment: 60
Actual Study Start Date: June 13, 2002
Primary Completion Date: June 1, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given orally
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva
Drug: Irinotecan Hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • Camptothecin 11
  • Camptothecin-11
  • CPT 11
  • CPT-11
  • Irinomedac
  • U-101440E

Detailed Description:


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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00045201

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Henry Pitot Mayo Clinic
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00045201     History of Changes
Obsolete Identifiers: NCT01646892, NCT01664286
Other Study ID Numbers: NCI-2009-00015
NCI-2009-00015 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
594-02 01
MC0112 ( Other Identifier: Mayo Clinic )
5351 ( Other Identifier: CTEP )
P30CA015083 ( US NIH Grant/Contract Award Number )
U01CA069912 ( US NIH Grant/Contract Award Number )
Study First Received: September 6, 2002
Last Updated: May 23, 2017

Additional relevant MeSH terms:
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors processed this record on May 25, 2017