Phase II (Treatment) Study of Oxaliplatin and Capecitabine in Advanced Head and Neck Malignancies

Study Overview
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Brief Summary
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This phase II study will test the response rate of combined oxaliplatin and capecitabine treatment when administered at a given dose and schedule, in patients with Head and Neck cancer for which there is no curative treatment.

Detailed Description
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The optimal dose and schedule for the combined treatment with oxaliplatin and capecitabine have not been defined. The aim of this Phase II study is to determine the response rate of combined oxaliplatin and capecitabine treatment at a given dose and schedule in patients with Head and Neck cancer for which there is no curative treatment. The study also aims to determine the qualitative and quantitative toxicity and reversibility of toxicity of the above combination and to evaluate any changes in performance status, quality of life, overall survival and progression-free survival.

Official Title
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Phase II Study of Oxaliplatin and Capecitabine in Advanced Head and Neck Malignancies

Conditions
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Head or Neck Cancer

Intervention / Treatment
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* Drug: Oxaliplatin, Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed squamous cell cancer of Head and Neck Patients must have metastatic or locally recurrent disease Patients must have disease not curable by surgery as estimated by one of the protocol investigators, and should not be eligible for reradiation protocol or have failed reradiation protocol. Patients must have 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 CT scan Age >18 years of age Life expectancy of greater than 12 weeks ECOG performance status 0, 1 or 2 (Karnofsky >50%; see Appendix B) Patients must have adequate bone marrow function as defined below: absolute neutrophil count > 1,500 platelets > 100,000 hemoglobin > 8 g/dl Patients must have adequate renal function as defined by a creatinine clearance >30 mL/min (measured or estimated by the Cockroft and Gault equation) Cockroft and Gault equation: Creatinine clearance for males =(140-age[yrs])(body wt[kg])/72(serum creatinine[mg/dL]) Creatinine clearance for females = 0.85 x male value Patients must have adequate liver function as defined below: total bilirubin 1.5x upper limit of normal albumin > 2.5 g/dl AST(SGOT) and ALT(SGPT) and Alkaline Phosphatase must be < 5 times upper limit of normal Patients could have received 1 or 2 previous chemotherapy regimens prior to entering the study. Patients must have recovered from acute toxicities from chemotherapy or radiotherapy administered prior to entering this study. Alopecia may not be resolved and peripheral neuropathy (grade 1) may be present. Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment. Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or oxaliplatin Patients who have had chemotherapy or radiotherapy within 4 weeks prior to first treatment in this study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier Patients receiving any other investigational agent(s) Patients with symptomatic brain metastases or actively receiving any therapy for brain metastasis (because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events) Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ Clinically significant cardiac disease (e.g. congestive heart failure, New York Heart Association Class II or greater, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months. If patient is unable to swallow, xeloda may be crushed per hospital policy/procedure. See attached Appendix G. Patients who have had an organ allograft. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnancy Known Hepatitis B , Hepatitis C, HIV Inclusion of Minorities: Members of all ethnic groups are eligible for this trial.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Study Drugs<br>Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. | Drug: Oxaliplatin, Capecitabine<br>* Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Among the 15 patients treated, 2 (13%) achieved partial response (PR), and 5 (33%) achieved stable disease (SD), for a Overall Response Rate (ORR) of 46% measured by RECIST criteria. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Overall Response Rate (ORR)=PR+CR. | Every two 28 day treatment cycles until subject no longer on treatment due to disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative and Quantitative Toxicity | Number of patients that developed common side effect of diarrhea. | At study enrollment, Every two 28 day treatment cycles, and at end of treatment due to disease progression |