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


Phase 2
18 Years
N/A
Not Enrolling
Both
Head and Neck Cancer

Thank you

Trial Information

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


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.

Inclusion Criteria


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)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

Michael K. Gibson, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000452784

NCT ID:

NCT00281866

Start Date:

July 2005

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • stage IV squamous cell carcinoma of the hypopharynx
  • stage IV squamous cell carcinoma of the larynx
  • stage IV squamous cell carcinoma of the lip and oral cavity
  • stage IV squamous cell carcinoma of the nasopharynx
  • stage IV squamous cell carcinoma of the oropharynx
  • stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
  • 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
  • recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
  • recurrent metastatic squamous neck cancer with occult primary
  • metastatic squamous neck cancer with occult primary squamous cell carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410