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

Head and Neck Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00281866
• Other study ID #: J0520 CDR0000452784
• Secondary ID: R21CA109283P30CA
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2006
• Last updated: October 10, 2016
• Start date: July 2005
• Est. completion date: March 2007

Study information

• Verified date: October 2016
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2007
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• erlotinib hydrochloride

Locations

Country	Name	City	State
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relationship between response rate and number of CA repeats in intron 1 of the EGFR			No
Secondary	Time to disease progression			No
Secondary	Survival			No
Secondary	Toxicity			Yes
Secondary	Compare the degree of p27 upregulation and EGFR phosphorylation in skin biopsy samples			No
Secondary	Relationship between erlotinib hydrochloride exposure and outcome, toxicity, and pharmacodynamic effects			Yes