Combination Chemotherapy With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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This randomized phase II trial studies how well combination chemotherapy with or without erlotinib hydrochloride works in treating patients with squamous cell carcinoma of the head and neck that has spread to other parts of the body or has come back. Drugs used in chemotherapy, such as docetaxel, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy with or without erlotinib hydrochloride may be an effective treatment for squamous cell carcinoma of the head and neck.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the efficacy of adding erlotinib hydrochloride (erlotinib) to chemotherapy to improve progression free survival in patients with metastatic or recurrent squamous cell carcinoma of the head and neck. SECONDARY OBJECTIVES: I. Evaluate overall survival, response rate, disease control rate, and duration of response by treatment with or without erlotinib. II. Evaluate quality of life (patient reported outcomes) by treatment with or without erlotinib. III. Evaluate the safety profile of erlotinib in combination with chemotherapy. IV. Correlate the occurrence of erlotinib-induced rash with outcomes. V. To evaluate the steady-state pharmacokinetics of erlotinib. VI. To explore the prognostic and predictive value of epidermal growth factor receptor related biomarkers and other biomarkers, including blood and tissue proteomic and blood and tissue genomic markers, that may be associated with clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive docetaxel intravenously (IV) over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1, and erlotinib hydrochloride orally (PO) daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment. ARM B: Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment. After completion of study treatment, patients are followed up at 30 days.

Official Title
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A Randomized, Placebo-Controlled, Phase 2 Study of Docetaxel and Cisplatin/Carboplatin With or Without Erlotinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck

Conditions
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Metastatic Squamous Cell Carcinoma of the Hypopharynx, Metastatic Squamous Cell Carcinoma of the Larynx, Metastatic Squamous Cell Carcinoma of the Oral Cavity, Metastatic Squamous Cell Carcinoma of the Oropharynx, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IV Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVC Hypopharyngeal Squamous Cell Carcinoma AJCC v7, Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7, Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7, Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Docetaxel
* Drug: Erlotinib Hydrochloride
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study
* Other: Placebo
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, hypopharynx or larynx; metastatic or recurrent lesions of the nasopharynx and sinus are excluded Radiologically measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; measurable lymph nodes are required to be >= 15 mm in size (short axis diameter) Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 Absolute neutrophil count (ANC) >= 1.5 x 10^9/L Platelet count >= 100 x 10^9/L Total bilirubin =< upper limit of normal (ULN) (excluding Gilbert's disease) Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN Alkaline phosphatase =< 2.5 x ULN Serum creatinine =< 1.5 x ULN Patients with reproductive potential (e.g., females menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures for the duration of study drug therapy and for at least 30 days after completion of study drug therapy; female patients of childbearing potential must provide a negative pregnancy test (serum or urine) =< 14 days prior to treatment initiation Written informed consent to participate in the study according to the investigational review board (IRB) or independent ethics committee (IEC) Exclusion Criteria: Histology other than squamous cell carcinoma Primary sites other than oral cavity, oropharynx, hypopharynx, and larynx Prior palliative chemotherapy for metastatic or recurrent disease Prior biological therapy for metastatic or recurrent disease within 3 weeks prior to randomization Patients with known, untreated brain metastases; patients with treated (irradiated or resected) brain metastases are eligible if treatment was completed more than 28 days prior to study entry and if clinical neurologic function is stable Pre-existing peripheral neuropathy >= grade 2 History of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g., Crohn's disease, ulcerative colitis); patients requiring feeding tubes are permitted Other active malignancies requiring chemotherapy treatment within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical or breast cancer or superficial, resected melanoma Serious underlying medical condition which would impair the ability of the patient to receive protocol treatment, in the opinion of the treating physician History of allergic reactions to compounds of similar chemical composition to the study drugs (docetaxel, cisplatin, carboplatin, erlotinib or their excipients), or other drugs formulated with polysorbate 80 Any concurrent anti-cancer therapy, excluding hormonal therapy for prostate or breast cancer Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent Women who are pregnant or breast-feeding and women or men not practicing effective birth control

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (combination chemotherapy and erlotinib hydrochloride)<br>Patients receive docetaxel IV over 1 hour and cisplatin IV over 2 hours or carboplatin IV over 2 hours on day 1 and erlotinib hydrochloride PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue erlotinib hydrochloride treatment. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Drug: Erlotinib Hydrochloride<br>* Given PO<br>* Other names: Tarceva;Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>Other: Pharmacological Study<br>* Optional correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Active Comparator: Arm B (combination chemotherapy and placebo)<br>Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression and unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue placebo treatment. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Cisplatin<br>* Given IV<br>* Other names: Platosin;Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Other: Laboratory Biomarker Analysis<br>* Optional correlative studies<br>Other: Pharmacological Study<br>* Optional correlative studies<br>Other: Placebo<br>* Given PO<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Kaplan-Meier methods will be used to summarize PFS. In the primary analysis, differences in PFS in Arm A versus Arm B will be tested using a stratified log-rank test with a two-sided alpha of 0.10. Hazard ratios for PFS will be presented using point estimates and 95% confidence intervals. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Kaplan-Meier methods will be used to summarize OS. Hazard ratios for OS will be presented using point estimates and 95% confidence intervals. | 5 years | 
| Number of Participants With Tumor Response (Complete Response [CR] + Partial Response [PR]) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions | 5 years | 
| Disease Control (CR + PR + Stable Disease [SD]) | Complete Response (CR) + Partial Response (PR) + Stable disease | 5 years | 
| Rash Rates | Participants with a Rash of at least grade 2 within cycle 1. | 5 years |