Head and Neck Cancer
Conditions
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
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.
Interventions
DRUGbortezomib
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.
DRUGdocetaxel
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.
OTHERlaboratory biomarker analysis
Tissue and blood collection.
OTHERpharmacological study
Blood collection.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Response to Treatment | 7.55 months (average duration, on study to off study) | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 7.55 months (average duration, on study to off study) | Median survival time of patients, calculated as on-study date to date of death or off-study date (censored) |
| Progression-free Survival | 7.55 months (average duration, on study to off study) | 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) |
Countries
United States
Participant flow
Recruitment details
This study was open to accrual from 8/25/2005 through 5/20/2008.
Pre-assignment details
Twenty-seven patients consented, two of which were ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib; Docetaxel Docetaxel will be given first at 40 mg/m2 IV on days 1 and 8 of a 21-day cycle except the first dose is held only on Day 1 of Cycle 1. Immediately afterwards, Bortezomib will be given at 1.6 mg/m2 IV 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. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Progression of disease | 18 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bortezomib; Docetaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age Continuous | 55 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 25 |
| serious Total, serious adverse events | 11 / 25 |
Outcome results
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.
Time frame: 7.55 months (average duration, on study to off study)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib; Docetaxel | Patient Response to Treatment | Partial Response | 1 participants |
| Bortezomib; Docetaxel | Patient Response to Treatment | Progressive Disease | 10 participants |
| Bortezomib; Docetaxel | Patient Response to Treatment | Stable Disease | 10 participants |
| Bortezomib; Docetaxel | Patient Response to Treatment | Not Evaluable | 4 participants |
Secondary
Overall Survival
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib; Docetaxel | Overall Survival | 5.13 Month |
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)
Time frame: 7.55 months (average duration, on study to off study)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bortezomib; Docetaxel | Progression-free Survival | 2.27 Month |