Erlotinib in Treating Patients With Metastatic and/or Recurrent Head and Neck Cancer

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00281866

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

18.5

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with recurrent and/or metastatic head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: erlotinib hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the relationship between response rate and number of CA repeats in intron 1 of the epidermal growth factor receptor (EGFR) in patients with metastatic and/or locally recurrent squamous cell carcinoma of the head and neck (SCCHN) treated with the EGFR inhibitor erlotinib hydrochloride.

Secondary

Determine the relationship between the number of CA repeats in intron 1 of the EGFR gene and time to disease progression and survival in patients treated with this drug.
Determine cutaneous and other toxicities of erlotinib hydrochloride in patients with different numbers of CA repeats in intron 1 of the EGFR gene.
Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples in patients with different numbers of CA repeats in intron 1 of the EGFR genes treated with this drug.
Determine the relationship between erlotinib hydrochloride exposure (utilizing total and unbound erlotinib hydrochloride concentrations) and outcome, toxicity, and pharmacodynamic effects (upregulation of p27) in patients with different numbers of CA repeats.

OUTLINE: This is a multicenter study. Patients are stratified according to genotype of intron 1 of the epidermal growth factor receptor (16/16 vs 16/20 or 20/20).

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

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

Non-Randomized

Primary Purpose:

Treatment

Official Title:

Genotypic-Based Pharmacodynamic Evaluation of Erlotinib (Erlotinib (Tarceva™, OSI Pharmaceuticals, Uniondale, NY) in Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Mar 1, 2007

Outcome Measures

Primary Outcome Measures

Relationship between response rate and number of CA repeats in intron 1 of the EGFR []

Secondary Outcome Measures

Time to disease progression []
Survival []
Toxicity []
Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples []
Relationship between erlotinib hydrochloride exposure and outcome, toxicity, and pharmacodynamic effects []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma of the head and neck
Metastatic and/or locally recurrent disease
No undifferentiated and nonkeratinizing carcinomas, including lymphoepitheliomas of all locations, as well as tumors of the parotid gland
WHO Type I squamous cell carcinoma of the nasopharynx are allowed
Incurable with surgery or radiotherapy
Measurable disease, defined as ≥ 1 target lesion ≥ 20 mm OR ≥ 10 mm on spiral CT scan
If the only site of measurable disease is in a previously irradiated area, the patient must have documented progressive disease by tomography or biopsy-proven residual carcinoma
No symptomatic brain metastases that are not stable, are not adequately controlled with fixed-dose oral steroids, are potentially life-threatening, or have required radiotherapy within the last 14 days

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Predicted life expectancy ≥ 12 weeks
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and/or ALT ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must practice effective contraceptive measures
No other prior malignancy within the past 3 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
No active or uncontrolled infection or other serious illnesses or medical conditions
No history of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No more than two prior chemotherapy regimens for locally recurrent and/or metastatic disease
Prior induction chemotherapy or chemoradiotherapy with curative intent for local disease allowed provided patient has received no more than two prior chemotherapy regimens for recurrent disease
Prior therapy must have been completed a minimum of 14 days prior to study AND patient has recovered
No prior molecular-directed therapies, such as tyrosine kinase inhibitors and/or monoclonal antibodies
At least 14 days must have elapsed between the end of radiotherapy and study registration and recovered
At least 14 days since prior surgery AND wound healing has occurred
At least 7 days since prior herbal extracts and tinctures with CYP3A inhibitory activity, including any of the following:
Hydrastis canadensis (goldenseal)
Uncaria tomentosa (cat's claw)
Echinacea angustifolia roots
Trifolium pratense (wild cherry)
Matricaria chamomilla (chamomile)
Glycyrrhiza glabra (licorice)
Dillapiol
Naringenin
No other concurrent anticancer therapy or other investigational agents
No concurrent administration of any of the following:
Phenytoin
Carbamazepine
Rifampicin
Barbiturates
Hypericum perforatum (St. John's wort)
CYP3A inhibitors (e.g., itraconazole)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
2	Hospital Universitario 12 de Octubre	Madrid		Spain	28041