Clinical trial NCT00425750: Bortezomib and Docetaxel in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Patient Response to Treatment
timeFrame: 7.55 months (average duration, on study to off study)
Secondary outcomes:
measure: Overall Survival
timeFrame: 7.55 months (average duration, on study to off study)
measure: Progression-free Survival
timeFrame: 7.55 months (average duration, on study to off study)
Other outcomes:
Locations:
city: Hopkinsville
country: United States
facility: Jennie Stuart Medical Center
state: Kentucky
city: Paducah
country: United States
facility: Purchase Cancer Group - Paducah
state: Kentucky
city: Crossville
country: United States
facility: Tennessee Plateau Oncology - Crossville
state: Tennessee
city: Jackson
country: United States
facility: West Tennessee Cancer Center at Jackson-Madison County General Hospital
state: Tennessee
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center at Baptist Riverside
state: Tennessee
city: Nashville
country: United States
facility: MBCCOP - Meharry Medical College - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Barbara Murphy, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.