Bortezomib and Docetaxel in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with docetaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with docetaxel works in treating patients with recurrent or metastatic head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Determine the overall response rate in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with bortezomib and docetaxel. Secondary Determine the time to progression in patients treated with this regimen. Determine the toxicity of this regimen. Determine the duration of response in patients treated with this regimen. Determine the overall survival and progression-free survival of these patients. Determine 20S proteasome inhibition in peripheral blood mononuclear cells (PBMC) from these patients. Determine the effect of bortezomib on NF-kB pathway in PBMC and serum samples. Identify biomarkers of clinical response to bortezomib and docetaxel in PBMC and serum. Determine quality of life, symptom burden, and physical function outcome in patients treated with this regimen. OUTLINE: This is a prospective, open-label, nonrandomized study. Patients receive docetaxel* IV over 30 minutes and bortezomib IV on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: *Docetaxel is not administered on day 1 of course 1. Blood samples are collected at baseline, after bortezomib administration on day 1 of course 1, and at the completion of treatment. The pharmacodynamics and pharmacogenomics of bortezomib are assessed in peripheral blood mononuclear cells (PBMC) and serum. After completion of study treatment, patients are followed every 6 weeks for 1 year and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Official Title
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Phase II Trial of Combination Weekly Bortezomib (VELCADE) and Docetaxel (TAXOTERE) in Patients With Recurrent and/ or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: bortezomib
* Drug: docetaxel
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx Recurrent or metastatic disease Measurable disease Not a candidate for curative therapy PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm³ Hemoglobin ≥ 8.0 g/dL Platelet count ≥ 100,000/mm³ AST, ALT, and alkaline phosphatase (AP) meeting 1 of the following criteria: AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST and ALT normal Bilirubin normal Creatinine clearance ≤ 2.0 mg/dL No peripheral neuropathy ≥ grade 2 within the past 28 days No myocardial infarction within the past 6 months No New York Heart Association class III or IV heart failure No uncontrolled angina No severe uncontrolled ventricular arrhythmias No electrocardiographic evidence of acute ischemia or active conduction system abnormalities No known hypersensitivity to bortezomib, boron, or mannitol No known severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 No serious medical or psychiatric illness that would preclude study participation No other malignancy within the past 3 years except for early-stage nonmelanomatous skin cancer, carcinoma in situ of the cervix, or early-stage prostate cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment PRIOR CONCURRENT THERAPY: No prior chemotherapy for recurrent or metastatic disease At least 28 days since prior and no other concurrent investigational drugs No other concurrent anticancer therapy No other concurrent chemotherapy No concurrent complementary or herbal medicine No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Docetaxel (40 mg/m2) IV Infusion over 30 minutes every 3 weeks (Day 1 and 8 of 21 day cycle)except the first dose is held on Day 1 of Cycle 1. Bortezomib (1.6mg/m2) IV 3-5 second push every 3 weeks (Day 1 and 8 of 21 day cycle).Bortezomib is given as a single agent only on Day 1 of Cycle 1. | Drug: bortezomib<br>* 1.6 mg/m2 through a vein on days 1 and 8 of a 21-day cycle. The first dose is given as a single agent only on Day 1 of Cycle 1.<br>Drug: docetaxel<br>* 40 mg/m2 through a vein on days 1 and 8 of a 21-day cycle except the first dose is held only on Day 1 of Cycle 1.<br>Other: laboratory biomarker analysis<br>* Tissue and blood collection.<br>Other: pharmacological study<br>* Blood collection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Response to Treatment | Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. | 7.55 months (average duration, on study to off study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Median survival time of patients, calculated as on-study date to date of death or off-study date (censored) | 7.55 months (average duration, on study to off study) | 
| Progression-free Survival | Median duration of survival without disease progression, calculated as on-study date to date of progression or date of death (censored) or off-study date (censored) | 7.55 months (average duration, on study to off study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx