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Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

Primary Purpose

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
erlotinib hydrochloride
docetaxel
radiation therapy
therapeutic conventional surgery
laboratory biomarker analysis
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma

Eligibility Criteria

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

Inclusion Criteria: Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease No prior chemotherapy, radiation therapy, or investigational anti-tumor drug Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria ECOG performance status =< 2 (Karnofsky >= 60%) Life expectancy of greater than 12 weeks Absolute neutrophil count >= 1,500/ul Platelets >= 100,000/ul Hemoglobin >= 10 mg/dL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 5 x ULN when alkaline phosphatase is =< ULN Alkaline phosphatase =< 5 x ULN when AST or ALT =< ULN Prothrombin time within normal institutional limits Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal No clinically significant heart disease (including 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) Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter; women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: All histologies other than squamous cell carcinoma Salivary gland and paranasal sinus squamous cell carcinoma Patients who have had prior chemotherapy or radiotherapy Patients may not be receiving any other investigational agents Patients with known brain metastases or direct cerebral invasion by tumor should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with intracranial extension (but without cerebral involvement) may still be eligible to participate History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or docetaxel, including other drugs formulated with polysorbate 80 No pre-existing peripheral neuropathy >= grade 2 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol HIV positive patients are excluded from participation Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient has remained continuously disease free Patients who are felt to be poorly compliant

Sites / Locations

  • Case Western Reserve University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (erlotinib hydrochloride, docetaxel, and radiation)

Arm Description

Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.

Outcomes

Primary Outcome Measures

MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I)
Pharmacokinetic profile (Phase I)
Time to disease progression (TTP) (Phase II)

Secondary Outcome Measures

Progression-free survival (PFS) (Phase II)
Will be estimated by Kaplan-Meier method.
Overall survival (OS) (Phase II)
Will be estimated by Kaplan-Meier method.
True objective response rate (Phase II)
Will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.
Changes of EGFR expression and serum markers over time (Phase II)
The Wilcoxon signed rank test (the non-parametric version of paired T-test) will be used.
Patterns of gene expression data (Phase II)
Cluster analysis including hierarchical clustering, Gaussian clustering, k means clustering, will be used.

Full Information

First Posted
November 12, 2002
Last Updated
June 5, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00049283
Brief Title
Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer
Official Title
A Phase I Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, 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
January 2013
Overall Recruitment Status
Completed
Study Start Date
September 2002 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with docetaxel may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells. Phase I trial to study the maximum tolerated dose (MTD) of combining erlotinib with docetaxel and radiation therapy in treating patients who have locally advanced head and neck cancer
Detailed Description
PRIMARY OBJECTIVES: I. Determine MTD and toxicity of combination of EGFR inhibitor (OSI-774), docetaxel, and radiation. II. Pharmacokinetic profile of OSI-774 alone and in combination with docetaxel. SECONDARY OBJECTIVES: I. Determine the overall and complete response rate of this combination. II. Determine overall, disease free, and progression free survival of this combination. EGFR expression and phosphorylation status Serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF Fluorescence in situ hybridization (FISH) for EGFR, ERBB2, PDGFR-β for gene amplification DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy material for mutation screening Gene expression profiling on pre-treatment biopsy material to identify predictors of response to treatment Apoptosis (TUNEL assay) Ki67 (nuclear proliferation antigen). OUTLINE: This is a dose-escalation study of erlotinib and docetaxel. Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete. Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24 weeks for 2 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, 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 Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer, Untreated Metastatic Squamous Neck Cancer With Occult Primary

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (erlotinib hydrochloride, docetaxel, and radiation)
Arm Type
Experimental
Arm Description
Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiotherapy
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo neck dissection
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I)
Time Frame
9 weeks
Title
Pharmacokinetic profile (Phase I)
Time Frame
Pre-dose, 0.5, 1, 2, 4, 8, 12, 24 48, and 72 hours
Title
Time to disease progression (TTP) (Phase II)
Time Frame
Up to 5.5 years
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS) (Phase II)
Description
Will be estimated by Kaplan-Meier method.
Time Frame
From the 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, assessed up to 5.5 years
Title
Overall survival (OS) (Phase II)
Description
Will be estimated by Kaplan-Meier method.
Time Frame
From the date of treatment to date of death, and to date of last follow-up for those still alive, assessed up to 5.5 years
Title
True objective response rate (Phase II)
Description
Will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.
Time Frame
Up to 5.5 years
Title
Changes of EGFR expression and serum markers over time (Phase II)
Description
The Wilcoxon signed rank test (the non-parametric version of paired T-test) will be used.
Time Frame
Baseline and up to 5.5 years
Title
Patterns of gene expression data (Phase II)
Description
Cluster analysis including hierarchical clustering, Gaussian clustering, k means clustering, will be used.
Time Frame
Up to 5.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease No prior chemotherapy, radiation therapy, or investigational anti-tumor drug Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria ECOG performance status =< 2 (Karnofsky >= 60%) Life expectancy of greater than 12 weeks Absolute neutrophil count >= 1,500/ul Platelets >= 100,000/ul Hemoglobin >= 10 mg/dL Total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) =< 5 x ULN when alkaline phosphatase is =< ULN Alkaline phosphatase =< 5 x ULN when AST or ALT =< ULN Prothrombin time within normal institutional limits Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal No clinically significant heart disease (including 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) Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter; women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: All histologies other than squamous cell carcinoma Salivary gland and paranasal sinus squamous cell carcinoma Patients who have had prior chemotherapy or radiotherapy Patients may not be receiving any other investigational agents Patients with known brain metastases or direct cerebral invasion by tumor should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with intracranial extension (but without cerebral involvement) may still be eligible to participate History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or docetaxel, including other drugs formulated with polysorbate 80 No pre-existing peripheral neuropathy >= grade 2 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol HIV positive patients are excluded from participation Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient has remained continuously disease free Patients who are felt to be poorly compliant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Panayiotis (Panos) Savvides
Organizational Affiliation
Case Western Reserve University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

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