Know Cancer

or
forgot password

A Pharmacogenetic and Pharmacodynamic Study of Erlotinib (OSI-774) Toxicity in Patients With Advanced Solid Tumors


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
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

Thank you

Trial Information

A Pharmacogenetic and Pharmacodynamic Study of Erlotinib (OSI-774) Toxicity in Patients With Advanced Solid Tumors


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism

Outcome 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.

Outcome Time Frame:

Baseline

Safety Issue:

Yes

Principal Investigator

Charles Rudin

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03097

NCT ID:

NCT00063895

Start Date:

April 2003

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Laryngeal Diseases
  • Lung Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms
  • Head and Neck Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470