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Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

Primary Purpose

Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
erlotinib hydrochloride
pharmacological study
pharmacogenomic studies
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients must have histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer, squamous cell carcinoma of the head and neck, or ovarian cancer Eligible patients must have been off previous anticancer therapy including chemotherapy, radiotherapy, biological therapy, or other investigational therapy for at least 4 weeks before study entry (6 weeks if prior therapy included nitrosoureas or mitomycin C) ECOG performance status =< 2 (Karnofsky >= 60%) Life expectancy of greater than 12 weeks Leukocytes >= 3,000/ul Absolute neutrophil count >= 1,500/ul Platelets >= 100,000/ul Total bilirubin within normal institutional limits Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must have measurable or assessable disease The effects of OSI-774 on the developing human fetus are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients with prior treatment with small molecule inhibitors of EGFR, including erlotinib and gefitinib, are not eligible for this study Patients may not be receiving any other investigational agents Patients with uncontrolled brain metastasis; patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because OSI-774 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with either agent HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Patients with significant ophthalmologic abnormalities, including: severe dry eye syndrome, kerato-conjunctivitis sicca, Sjogren's syndrome, severe exposure keratopathy, disorders that might increase the risk for epithelium-related complications (e.g. bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis); patients with mild forms of any of the above, an asymptomatic history, or a normal ophthalmologic examination may be considered for inclusion at the discretion of the investigator; an ophthalmologic exam is not needed prior to this study unless clinically indicated; patients with treatable conditions (e.g. infectious keratitis/conjunctivitis, allergic conjunctivitis) may be reevaluated for study eligibility after treatment or resolution of the condition; use of contact lenses during the course of this trial may increase the risk of corneal complications and will be strongly discouraged Serious, non-healing wound ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 14 days prior to Day 1; following such procedures or injuries, wound healing should be evident prior to initiation of therapy

Sites / Locations

  • University of Chicago Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (erlotinib hydrochloride)

Arm Description

Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.

Secondary Outcome Measures

Pharmacodynamic effects of erlotinib hydrochloride on EGFR activity and MAP kinase signaling
Observed anti-tumor responses
Number of patients with complete or partial tumor responses and will be tabulated; 95% confidence intervals will be generated.
All observed toxicities
The frequency of adverse events will be tabulated; 95% confidence intervals will be generated.
Erlotinib hydrochloride AUC
Compared with incidence of toxicity in patients with at least one 3A5*1 allele to those with no 3A5*1 allele using two-sample t and chi square tests, respectively. The relationship between toxicity and AUC evaluated by fitting ordinal (proportional odds) logistic regression models in which the grade of toxicity is the dependent variable and AUC is the independent or predictor variable. If the proportional odds model does not provide a good fit to the data then the toxicity grade will be dichotomized and analyzed using and analyzed using ordinary logistic regression.

Full Information

First Posted
July 8, 2003
Last Updated
January 8, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00063895
Brief Title
Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck
Official Title
A Pharmacogenetic and Pharmacodynamic Study of Erlotinib (OSI-774) Toxicity in Patients With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase I/II trial is studying the side effects of erlotinib and to see how well it works in treating patients with metastatic or unresectable non-small cell lung cancer, ovarian cancer, or squamous cell carcinoma (cancer) of the head and neck. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth
Detailed Description
PRIMARY OBJECTIVES: I. To determine if a significant correlation exists between the length of the CA dinucleotide repeat polymorphism in the EGFR gene and observed toxicity in patients treated with OSI-774. SECONDARY OBJECTIVES: I. To study the pharmacodynamic effects of OSI-774 on EGFR activity and MAP kinase signaling using skin as a surrogate tissue. II. To determine if interindividual variation of OSI-774 pharmacokinetics is related to a previously described CYP3A5 genetic polymorphism. III. To evaluate whether toxicity or inhibition of EGFR phosphorylation correlates with OSI-774 AUC in patients treated with OSI-774. IV. To describe the observed anti-tumor response and toxicities in patients with advanced solid tumors treated with single agent fixed dose of OSI-774. OUTLINE: This is a multicenter study. Patients are stratified according to length of CA dinucleotide repeat polymorphism (short vs medium vs long). Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IIIA Non-small Cell Lung Cancer, Stage IIIA Ovarian Epithelial Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IIIB Ovarian Epithelial Cancer, Stage IIIC Ovarian Epithelial Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (erlotinib hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacogenomic studies
Other Intervention Name(s)
Pharmacogenomic Study
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Description
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
Time Frame
Baseline
Title
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
Description
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Pharmacodynamic effects of erlotinib hydrochloride on EGFR activity and MAP kinase signaling
Time Frame
Week 1
Title
Observed anti-tumor responses
Description
Number of patients with complete or partial tumor responses and will be tabulated; 95% confidence intervals will be generated.
Time Frame
Up to 4 years
Title
All observed toxicities
Description
The frequency of adverse events will be tabulated; 95% confidence intervals will be generated.
Time Frame
Up to 4 years
Title
Erlotinib hydrochloride AUC
Description
Compared with incidence of toxicity in patients with at least one 3A5*1 allele to those with no 3A5*1 allele using two-sample t and chi square tests, respectively. The relationship between toxicity and AUC evaluated by fitting ordinal (proportional odds) logistic regression models in which the grade of toxicity is the dependent variable and AUC is the independent or predictor variable. If the proportional odds model does not provide a good fit to the data then the toxicity grade will be dichotomized and analyzed using and analyzed using ordinary logistic regression.
Time Frame
Baseline, 0.5, 1, 2, 4, and 6 h after initiation, and pre-treatment days 15 and 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer, squamous cell carcinoma of the head and neck, or ovarian cancer Eligible patients must have been off previous anticancer therapy including chemotherapy, radiotherapy, biological therapy, or other investigational therapy for at least 4 weeks before study entry (6 weeks if prior therapy included nitrosoureas or mitomycin C) ECOG performance status =< 2 (Karnofsky >= 60%) Life expectancy of greater than 12 weeks Leukocytes >= 3,000/ul Absolute neutrophil count >= 1,500/ul Platelets >= 100,000/ul Total bilirubin within normal institutional limits Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must have measurable or assessable disease The effects of OSI-774 on the developing human fetus are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients with prior treatment with small molecule inhibitors of EGFR, including erlotinib and gefitinib, are not eligible for this study Patients may not be receiving any other investigational agents Patients with uncontrolled brain metastasis; patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because OSI-774 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with either agent HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated Patients with significant ophthalmologic abnormalities, including: severe dry eye syndrome, kerato-conjunctivitis sicca, Sjogren's syndrome, severe exposure keratopathy, disorders that might increase the risk for epithelium-related complications (e.g. bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis); patients with mild forms of any of the above, an asymptomatic history, or a normal ophthalmologic examination may be considered for inclusion at the discretion of the investigator; an ophthalmologic exam is not needed prior to this study unless clinically indicated; patients with treatable conditions (e.g. infectious keratitis/conjunctivitis, allergic conjunctivitis) may be reevaluated for study eligibility after treatment or resolution of the condition; use of contact lenses during the course of this trial may increase the risk of corneal complications and will be strongly discouraged Serious, non-healing wound ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 14 days prior to Day 1; following such procedures or injuries, wound healing should be evident prior to initiation of therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Rudin
Organizational Affiliation
University of Chicago Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States

12. IPD Sharing Statement

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Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

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