Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck

Phase 2

Completed

• Conditions: Head and Neck Cancer
• Interventions: Drug: docetaxel; Drug: erlotinib hydrochloride; Genetic: fluorescence in situ hybridization; Genetic: polymerase chain reaction; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: therapeutic conventional surgery; Radiation: intensity-modulated radiation therapy; Radiation: radiation therapy

• Registration Number: NCT00720304
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with docetaxel and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well erlotinib given together with docetaxel and radiation therapy works in treating patients with stage III or stage IV squamous cell carcinoma of the head and neck.

Detailed Description

OBJECTIVES:

Primary

* Determine the time to progression in patients with locally advanced squamous cell carcinoma of the head and neck treated with erlotinib hydrochloride in combination with docetaxel and radiotherapy.

Secondary

* Determine objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival in patients treated with this regimen.

* Determine the toxicities of this regimen in these patients.

* Determine the dose and effect of this treatment on biologic correlates in tumor tissue and/or surrounding mucosa.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Beginning on week 3, patients receive docetaxel IV over 1 hour once a week and radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery. Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.

Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.

After completion of study therapy, patients will be evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.

Study Timeline

• Study Start: 2007-11-19
• Study First Submitted: 2008-07-19
• Study First Submitted QC: 2008-07-19
• Study First Posted: 2008-07-22
• Primary Completion: 2015-11-13
• Study Completion: 2015-11-13
• Results First Submitted: 2021-11-19
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-19
• Last Update Submitted: 2024-08-19
• Results First Posted: 2024-08-22
• Last Update Posted: 2024-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
oral erlotinib hydrochloride	polymerase chain reaction	-
oral erlotinib hydrochloride	erlotinib hydrochloride	-
oral erlotinib hydrochloride	therapeutic conventional surgery	-
oral erlotinib hydrochloride	immunohistochemistry staining method	-
oral erlotinib hydrochloride	intensity-modulated radiation therapy	-
oral erlotinib hydrochloride	radiation therapy	-
oral erlotinib hydrochloride	fluorescence in situ hybridization	-
oral erlotinib hydrochloride	laboratory biomarker analysis	-
oral erlotinib hydrochloride	pharmacological study	-
oral erlotinib hydrochloride	immunoenzyme technique	-
oral erlotinib hydrochloride	docetaxel	-

Primary Outcome Measures

Name	Time	Method
Percent of Participants With Disease-Free Survival (DFS) at 3 Years	3 yrs after treatment	Percent of participants with Disease-Free survival (DFS) at 3 years. Assessed from date of treatment to date of death or date of disease progression, and to date of last follow-up for those still alive and progression free. Disease-free Survival percentages were calculated using Kaplan-Meier estimates.
Time to Progression (TTP)	3 yrs after treatment	Time from start of treatment to first documented occurrence of progressive disease (PD). PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

Name	Time	Method
Percent of Participants With Regional Failure-free Survival	At 3 years	Participants with the regional absence of relapse or recurrence or progression within the prescribed radiation field. Failure-free Survival percentages were calculated using Kaplan-Meier estimates.
Percent of Participants With Locoregional Failure-free Survival	At 3 years	Participants with the locoregional absence of relapse or recurrence or progression within the prescribed radiation field. Locoregional failure-free survival percentages were calculated using Kaplan-Meier estimates.
Overall Survival (OS)	3 years	Percent of participants alive at follow-up time. Overall survival time is evaluated from the date of treatment to date of death, and to date of last follow-up for those still alive.
Number of Participants With Acute Grade III/IV Treatment-related Toxicities	evaluated every 2 weeks, up to 3 years	Number of participants with acute grade III/IV treatment-related toxicities
Response Rate (Complete Response, Partial Response, Stable Disease, and Disease Progression)	3 yrs after treatment	Response rate according to response criteria, which defines the following: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Percent of Participants With Local Failure-free Survival	At 3 years	Participants with Local absence of relapse or recurrence or progression within the prescribed radiation field.
Percent of Participants With Distant Metastasis-free Survival	At 3 years	Percent of participants with distant metastasis-free survival

Trial Locations

Locations (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States