Docetaxel and Capecitabine for First Line Treatment of Metastatic Squamous Cell Carcinoma of the Head & Neck

Study Overview
=================
Brief Summary
-----------------
Recent progress in treatment of recurrent/metastatic SCCHN has been made with the introduction of the taxanes. Docetaxel as a single agent has a response rate of 22-42% and 17% in patients with recurrent disease. Capecitabine is an oral fluoropyrimidine prodrug that is converted into 5-FU. Previous studies have shown that the capecitabine/docetaxel combination has a synergistic inhibition of tumor growth, resulting in significantly superior efficacy in time to disease progression (TTP), overall survival, median survival and objective tumor response rate compared to docetaxel alone. This trial will investigate the efficacy the combination of docetaxel and capecitabine in treating patients with recurrent/metastatic SCCHN.

Detailed Description
-----------------
OUTLINE: This is a multi-center study. Dexamethasone and antiemetic premedication1. Docetaxel: 60 mg/m2 for a 60 minute infusion day 1 of each cycle Capecitabine: 825 mg/m2 po BID Days 1-14 Repeat every 21 days until tumor progression or toxicity that requires discontinuation of therapy Performance status: ECOG performance status 0 or 1 Life expectancy: At least 3 months Hematopoietic: ANC of > 1,500/mm3 Platelets > 100,000/mm3 Hemoglobin > 8 gm/dl Hepatic: Total Bilirubin £ ULN Albumin > 3 Maximum Alk Phos > 2.5 x < 5 x ULN Renal: Creatinine clearance of > 50 ml/ min (by Cockcroft-Gault) Cardiovascular: No decompensated congestive heart failure or active angina. Clinically significant cardiac disease not well controlled with medication (eg. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction in the past 12 months is not allowed. Pulmonary: Not specified

Official Title
-----------------
A Single Arm Phase II Trial of Docetaxel and Capecitabine for the First Line Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN): Hoosier Oncology Group HN02-40

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: Capecitabine
* Drug: Premedication


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck. Recurrent/metastatic disease not amenable to surgery or salvage chemoradiation. Unidimensional measurable disease according to the RECIST In-field recurrence, within a prior radiation field only, distant metastatic disease Both in-field and metastatic sites of disease will require evaluation by a Radiation Oncologist to consider local radiation therapy first and will be eligible for possible enrollment one month after completion of the radiation therapy. Negative pregnancy test Patients may have received prior chemotherapy as part of chemoradiation or induction chemotherapy for initial treatment of disease confined to the head and neck region - Patients must have fully recovered from any prior radiation therapy Exclusion Criteria: Patients who have relapsed < 6 months after completing a combined modality curative treatment that included a fluoropyrimidine or taxanes No brain metastases No major neurological disease, including stroke No prior chemotherapy regimen for recurrent/metastatic disease No prior history of capecitabine usage No prior history of docetaxel usage except in the induction setting for head and neck cancer which has been completed for greater than 6 months prior to beginning protocol therapy No past hypersensitivity to taxanes or 5 FU No hypersensitivity to docetaxel or other drugs formulated with polysorbate 80 No current use of warfarin Patients must not be receiving ketoconazole, midazolam, erythromycin, orphenadrine, troleandomycin, cyclosporine or antiepileptics Patients must not be treated with any of the following on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol Patients must have fully recovered from any prior surgery No known HIV seropositivity. No serious uncontrolled medical condition, uncontrolled peptic ulcer disease or malabsorption syndrome No peripheral neuropathy > grade 1 Patients with a percutaneous gastrostomy (PEG) must be able take medications by tube. No daily consumption of alcohol No active infection No prior history of malignancy in the last 5 years, excluding in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin or Gleason Grade < VII organ confined prostate cancer. No current breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Docetaxel + Capecitabine | Drug: Docetaxel<br>* Docetaxel 60 mg/m2 for 60 minutes, day 1 of each cycle<br>Drug: Capecitabine<br>* Capecitabine 825 mg/m2 po bid, days 1-14<br>Drug: Premedication<br>* Dexamethasone and antiemetic premedication<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - To assess response rate in a group of patients receiving combination therapy with docetaxel and capecitabine |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess toxicity of the combination |  | 24 months | 
| To determine whether the status of calpain, calpain activation,(EGFR) expression, Cox-2 expression, TS, TP, DPD, and/or CYP3A4/CYP3A5 will predict treatment |  | 24 months | 
| Efficacy and safety analyses on special sub-cohorts |  | 24 months | 
| To determine the progression free survival and overall survival |  | 24 months | 
| To assess change in analgesic usage with this protocol therapy |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Head and Neck Cancer