Erlotinib Plus Docetaxel in Treating Patients With Locally Advanced, Metastatic, or Recurrent Head and Neck Cancer

Stage IV Squamous Cell Carcinoma of the Hypopharynx Clinical Trial

Official title:

A Phase I and Phase II Study of OSI-774 in Combination With Docetaxel in Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055770
• Other study ID #: NCI-2012-01432
• Secondary ID: NCI-2012-01432OS
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 6, 2003
• Last updated: November 21, 2013
• Start date: October 2002

Study information

• Verified date: November 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase I/II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have locally advanced, recurrent, or metastatic head and neck cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells.

Description:

OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered in combination with docetaxel in patients with locally advanced, metastatic, or recurrent squamous cell carcinoma of the head and neck.

II. Determine the response rate, duration of response, time to progression, and survival of patients treated with this regimen.

III. Determine the pharmacokinetics of this regimen in these patients. IV. Correlate the presence of PTEN, RB, P-Akt, p15, p16, cyclin D1, p27, and p53 genes in tumor tissue with response in patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of erlotinib followed by a phase II study.

PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.

PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck meeting 1 of the following staging criteria:

• Recurrent

• Metastatic

• Locally advanced and determined to be incurable by surgery or radiotherapy

• Measurable disease

• No known brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin normal

• AST and ALT no greater than 2.5 times upper limit of normal

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No severe pulmonary insufficiency, including chronic obstructive pulmonary disease, requiring oxygen (O2 saturation less than 90%) and/or increase in PaCO2 blood gas level greater than 50 mm Hg

• No history of abnormality of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

• No congenital abnormality (e.g., Fuch's dystrophy)

• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)

• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

• Able to take oral medication

• No requirement for IV alimentation

• No active peptic ulcer disease

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No significant traumatic injury within the past 21 days

• No prior allergic reactions to compounds of similar chemical or biological composition to study drugs

• No grade 2 or greater persistent peripheral neuropathy

• No other concurrent uncontrolled illness that would preclude study participation

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance

• No prior immunotherapy for head and neck cancer

• No more than 1 prior chemotherapy regimen in the adjuvant or neoadjuvant setting

• No more than 1 prior chemotherapy regimen for metastatic disease

• No prior docetaxel (phase II only)

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No prior hormonal therapy for head and neck cancer

• Prior external beam radiotherapy allowed

• At least 4 weeks since prior radiotherapy and recovered

• More than 21 days since prior major surgery

• No prior surgery affecting gastrointestinal absorption

• No prior epidermal growth factor receptor-targeting therapy

• No other concurrent investigational agents

• No other concurrent anticancer therapies or agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Laryngeal Diseases
• Laryngeal Neoplasms
• Nasopharyngeal Neoplasms
• Oropharyngeal Neoplasms
• Paranasal Sinus Neoplasms
• Recurrent Salivary Gland 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
• Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Salivary Gland Neoplasms
• Salivary Gland Squamous Cell Carcinoma
• Stage III Salivary Gland Cancer
• 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 III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Stage IV Salivary Gland 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

Intervention

Drug:
• erlotinib hydrochloride
Given orally
• docetaxel
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of erlotinib and docetaxel, based on incidence of DLT graded according to NCI CTC version 2.0 (Phase I)		Up to 28 days	Yes
Primary	Proportion of patients with an objective response (Phase II)		Up to 6 years	No
Secondary	Response rate as measured by RECIST criteria (Phase II)		Up to 6 years	No
Secondary	Time to tumor progression (Phase II)		Up to 6 years	No
Secondary	Median survival (Phase II)		Up to 6 years	No