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

NCT ID: NCT00425750

Last Updated: 2011-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2009-06-30

Brief Summary

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

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

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.

Group Type: EXPERIMENTAL

bortezomib

Intervention Type: DRUG

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.

docetaxel

Intervention Type: DRUG

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.

laboratory biomarker analysis

Intervention Type: OTHER

Tissue and blood collection.

pharmacological study

Intervention Type: OTHER

Blood collection.

Interventions

bortezomib

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.

Intervention Type: DRUG

docetaxel

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.

Intervention Type: DRUG

laboratory biomarker analysis

Tissue and blood collection.

Intervention Type: OTHER

pharmacological study

Blood collection.

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Barbara Murphy

Professor of Medicine; Director, Cancer Supportive Care Program; Director, Head and Neck Research Program; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barbara Murphy, MD

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

Jennie Stuart Medical Center

Hopkinsville, Kentucky, United States

Purchase Cancer Group - Paducah

Paducah, Kentucky, United States

Tennessee Plateau Oncology - Crossville

Crossville, Tennessee, United States

West Tennessee Cancer Center at Jackson-Madison County General Hospital

Jackson, Tennessee, United States

Baptist Regional Cancer Center at Baptist Riverside

Knoxville, Tennessee, United States

MBCCOP - Meharry Medical College - Nashville

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

Chung CH, Aulino J, Muldowney NJ, Hatakeyama H, Baumann J, Burkey B, Netterville J, Sinard R, Yarbrough WG, Cmelak AJ, Slebos RJ, Shyr Y, Parker J, Gilbert J, Murphy BA. Nuclear factor-kappa B pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2010 Apr;21(4):864-870. doi: 10.1093/annonc/mdp390. Epub 2009 Oct 22.

Reference Type: RESULT

PMID: 19850643 (View on PubMed)

Chung CH, Lee JW, Slebos RJ, Howard JD, Perez J, Kang H, Fertig EJ, Considine M, Gilbert J, Murphy BA, Nallur S, Paranjape T, Jordan RC, Garcia J, Burtness B, Forastiere AA, Weidhaas JB. A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2014 Nov;25(11):2230-2236. doi: 10.1093/annonc/mdu367. Epub 2014 Jul 31.

Reference Type: DERIVED

PMID: 25081901 (View on PubMed)

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-HN-0501

Identifier Type: -

Identifier Source: secondary_id

MILLENIUM-X05170

Identifier Type: -

Identifier Source: secondary_id

VU-VICC-IRB-050183

Identifier Type: -

Identifier Source: secondary_id

VICC HN 0501

Identifier Type: -

Identifier Source: org_study_id