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

Head and Neck Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425750
• Other study ID #: VICC HN 0501
• Secondary ID: P30CA068485VU-VI
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2007
• Last updated: November 7, 2011
• Start date: August 2005
• Est. completion date: June 2009

Study information

• Verified date: November 2011
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• 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.
• 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.

Other:
• laboratory biomarker analysis
Tissue and blood collection.
• pharmacological study
Blood collection.

Locations

Country	Name	City	State
United States	Tennessee Plateau Oncology - Crossville	Crossville	Tennessee
United States	Jennie Stuart Medical Center	Hopkinsville	Kentucky
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	Purchase Cancer Group - Paducah	Paducah	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 doc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No