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

Vanderbilt University Medical Center

Status and phase: Completed; Phase 2

Conditions: Head and Neck Cancer

Treatments: Other: pharmacological study; Drug: docetaxel; Drug: bortezomib; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00425750

VU-VICC-HN-0501

P30CA068485 (U.S. NIH Grant/Contract)

VICC HN 0501

VU-VICC-IRB-050183

MILLENIUM-X05170

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Treatment

Experimental group

Description:

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.

Treatment:

Other: pharmacological study

Drug: docetaxel

Other: laboratory biomarker analysis

Drug: bortezomib