Clinical trial NCT00281866: Erlotinib in Treating Patients With Metastatic and/or Recurrent Head and Neck Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-25
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Relationship between response rate and number of CA repeats in intron 1 of the EGFR
Secondary outcomes:
measure: Time to disease progression
measure: Survival
measure: Toxicity
measure: Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples
measure: Relationship between erlotinib hydrochloride exposure and outcome, toxicity, and pharmacodynamic effects
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Michael K. Gibson, MD
role: STUDY_CHAIR
References: