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

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

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.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Docetaxel; Drug: Premedication

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

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F. Graham Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart Clinic
    • Evansville, Indiana, United States, 47714
      • Oncology Hematology Associates of SW Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Goshen, Indiana, United States, 46527
      • Center for Cancer Care at Goshen Health System
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Quality Cancer Center (MCGOP)
    • Lafayette, Indiana, United States, 47904
      • Arnett Cancer Care
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • New Albany, Indiana, United States, 47150
      • Center for Cancer Care, Inc., P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
    • Terre Haute, Indiana, United States, 47802
      • Providence Medical Group
    • Terre Haute, Indiana, United States, 47804
      • AP&S Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Michigan
    • Jackson, Michigan, United States, 49201
      • Center for Hematology-Oncology of S Michigan
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Docetaxel + Capecitabine	Drug: Capecitabine; Capecitabine 825 mg/m2 po bid, days 1-14; Drug: Docetaxel; Docetaxel 60 mg/m2 for 60 minutes, day 1 of each cycle; Drug: Premedication; Dexamethasone and antiemetic premedication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Sanofi; Hoffmann-La Roche; Walther Cancer Institute
• Investigators: Study Chair: David Potter, M.D., Hoosier Oncology Group, LLC

Publications and helpful links

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (ACTUAL): September 1, 2007
• Study Completion (ACTUAL): September 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (ESTIMATE): September 22, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): May 2, 2011
• Last Update Submitted That Met QC Criteria: April 28, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Head and Neck Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Capecitabine
• Other Study ID Numbers: HOG HN02-40