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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
docetaxel
laboratory biomarker analysis
pharmacological study
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Jennie Stuart Medical Center
  • Purchase Cancer Group - Paducah
  • Tennessee Plateau Oncology - Crossville
  • West Tennessee Cancer Center at Jackson-Madison County General Hospital
  • Baptist Regional Cancer Center at Baptist Riverside
  • MBCCOP - Meharry Medical College - Nashville
  • Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall Survival
Median survival time of patients, calculated as on-study date to date of death or off-study date (censored)
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)

Full Information

First Posted
January 19, 2007
Last Updated
November 7, 2011
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00425750
Brief Title
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

2. Study Status

Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Description
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
Intervention Name(s)
docetaxel
Intervention Description
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
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Tissue and blood collection.
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Description
Blood collection.
Primary Outcome Measure Information:
Title
Patient Response to Treatment
Description
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.
Time Frame
7.55 months (average duration, on study to off study)
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Median survival time of patients, calculated as on-study date to date of death or off-study date (censored)
Time Frame
7.55 months (average duration, on study to off study)
Title
Progression-free Survival
Description
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)
Time Frame
7.55 months (average duration, on study to off study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Murphy, MD
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Jennie Stuart Medical Center
City
Hopkinsville
State/Province
Kentucky
ZIP/Postal Code
42240-2400
Country
United States
Facility Name
Purchase Cancer Group - Paducah
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42001
Country
United States
Facility Name
Tennessee Plateau Oncology - Crossville
City
Crossville
State/Province
Tennessee
ZIP/Postal Code
38555
Country
United States
Facility Name
West Tennessee Cancer Center at Jackson-Madison County General Hospital
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38301
Country
United States
Facility Name
Baptist Regional Cancer Center at Baptist Riverside
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37901
Country
United States
Facility Name
MBCCOP - Meharry Medical College - Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37208-3599
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19850643
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.
Results Reference
result
PubMed Identifier
25081901
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. Erratum In: Ann Oncol. 2015 May;26(5):1038-9.
Results Reference
derived

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

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