search
Back to results

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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
docetaxel
erlotinib hydrochloride
fluorescence in situ hybridization
polymerase chain reaction
immunoenzyme technique
immunohistochemistry staining method
laboratory biomarker analysis
pharmacological study
therapeutic conventional surgery
intensity-modulated radiation therapy
radiation therapy
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck

    • Stage III or IV disease

      • No distant metastatic disease
  • Measurable disease (according to RECIST)
  • No salivary gland and paranasal sinus squamous cell carcinoma

  • No known brain metastases or direct cerebral invasion by tumor

    • Intracranial extension (without cerebral involvement) may be allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥10 g/dL
  • Total bilirubin normal

  • Alkaline phosphatase AND AST and ALT meeting the following criteria:

    • Alkaline phosphatase normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2.5 times ULN AND AST and ALT ≤ 2.5 times ULN
    • Alkaline phosphatase ≤ 5 times ULN AND AST and ALT normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min

  • No clinically significant heart disease including any of the following:

    • NYHA class III or IV heart disease
    • Significant arrhythmias requiring medication
    • Symptomatic coronary artery disease
    • Myocardial infarction within the previous six months
    • Second- or third-degree heart block or bundle-branch block
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80
  • No pre-existing peripheral neuropathy ≥ grade 2

  • No uncontrolled concurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would preclude compliance with study requirements
  • No HIV positivity

  • No other prior malignancy except for any of the following:

    • Squamous cell or basal cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Cancer that was treated more than 5 years ago and the patient has remained disease-free
  • Not poorly compliant

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or investigational antitumor drug
  • No other concurrent investigational agents

Sites / Locations

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

oral erlotinib hydrochloride

Arm Description

Outcomes

Primary Outcome Measures

Progression-free-survival
Time to progression

Secondary Outcome Measures

Response rate (complete response, partial response, stable disease, and disease progression)
Overall survival
Toxicities
Predictive values of EGFR/TGF-α, VEGF

Full Information

First Posted
July 19, 2008
Last Updated
November 25, 2015
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00720304
Brief Title
Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck
Official Title
A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
oral erlotinib hydrochloride
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Description
Beginning on week 3, patients receive docetaxel IV over 1 hour once a week
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Intervention Description
oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity
Intervention Type
Genetic
Intervention Name(s)
fluorescence in situ hybridization
Intervention Description
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.
Intervention Type
Genetic
Intervention Name(s)
polymerase chain reaction
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
immunoenzyme technique
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Intervention Description
radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Progression-free-survival
Time Frame
3 yrs after treatment
Title
Time to progression
Time Frame
3 yrs after treatment
Secondary Outcome Measure Information:
Title
Response rate (complete response, partial response, stable disease, and disease progression)
Time Frame
3 yrs after treatment
Title
Overall survival
Time Frame
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.
Title
Toxicities
Time Frame
evaluated every 2 weeks
Title
Predictive values of EGFR/TGF-α, VEGF
Time Frame
collection at baseline and periodically during study.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck Stage III or IV disease No distant metastatic disease Measurable disease (according to RECIST) No salivary gland and paranasal sinus squamous cell carcinoma No known brain metastases or direct cerebral invasion by tumor Intracranial extension (without cerebral involvement) may be allowed PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% Life expectancy > 12 weeks ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥10 g/dL Total bilirubin normal Alkaline phosphatase AND AST and ALT meeting the following criteria: Alkaline phosphatase normal AND AST and ALT ≤ 5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN AND AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 5 times ULN AND AST and ALT normal Creatinine normal OR creatinine clearance ≥ 60 mL/min No clinically significant heart disease including any of the following: NYHA class III or IV heart disease Significant arrhythmias requiring medication Symptomatic coronary artery disease Myocardial infarction within the previous six months Second- or third-degree heart block or bundle-branch block Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80 No pre-existing peripheral neuropathy ≥ grade 2 No uncontrolled concurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness/social situations that would preclude compliance with study requirements No HIV positivity No other prior malignancy except for any of the following: Squamous cell or basal cell carcinoma of the skin Carcinoma in situ of the cervix Cancer that was treated more than 5 years ago and the patient has remained disease-free Not poorly compliant PRIOR CONCURRENT THERAPY: No prior chemotherapy, radiotherapy, or investigational antitumor drug No other concurrent investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Min Yao, MD
Organizational Affiliation
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs