Head and Neck Cancer
Conditions
Keywords
stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx
Brief summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with docetaxel and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with docetaxel and radiation therapy works in treating patients with stage III or stage IV head and neck cancer.
Detailed description
OBJECTIVES: Primary * Determine the time to progression in patients with stage III or IV squamous cell carcinoma of the head and neck treated with bevacizumab in combination with docetaxel and radiotherapy. Secondary * Compare the objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: Patients undergo radiotherapy once daily, 5 days a week, for 8 weeks and receive docetaxel IV over 1 hour once a week for 8 weeks. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks for up to 1 year. Approximately 8-10 weeks after the completion of chemoradiotherapy, patients may undergo neck dissection. Bevacizumab, which stops 8 weeks before surgery, may restart 4 weeks after surgery and continue for 9 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Interventions
BIOLOGICALbevacizumab
Bevacizumab IV over 30-90 minutes once every 2 weeks for up to 1 year. Bevacizumab, which stops 8 weeks before surgery, may restart 4 weeks after surgery and continue for 9 months in the absence of disease progression or unacceptable toxicity.
DRUGdocetaxel
docetaxel IV over 1 hour once a week for 8 weeks
PROCEDUREconventional surgery
8-10 weeks after the completion of chemoradiotherapy, patients may undergo neck dissection
RADIATIONradiation therapy
radiotherapy once daily, 5 days a week, for 8 weeks
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
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: * Histologically or cytologically confirmed squamous cell carcinoma of the head and neck * Stage III or IV disease * No evidence of distant metastases * No salivary gland or paranasal sinus squamous cell carcinoma * No disease with close proximity to a major vessel * Measurable disease * No known CNS or brain metastases * Patients with intracranial extension without cerebral involvement may be eligible PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy \> 12 weeks * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * Bilirubin normal * AST and ALT ≤ 2 times upper limit of normal * PT normal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min * Urine protein: creatinine ratio \< 1.0 * No bleeding diathesis or coagulopathy * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs * No pre-existing peripheral neuropathy ≥ grade 2 * No ongoing or active infection * No serious non-healing wound, ulcer, or bone fracture * No New York Heart Association class II-IV congestive heart failure * No significant arrhythmias requiring medication * No myocardial infarction within the past 6 months * No stroke within the past 6 months * No symptomatic coronary artery disease * No second- or third-degree heart block or bundle branch block * No unstable angina pectoris * No hypertension (i.e., blood pressure ≥ 150/100 mm Hg) * No other clinically significant heart disease * No significant traumatic injury within the past 4 weeks * No psychiatric illness or social situation that would preclude study compliance * No HIV positivity * No other malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix * No other uncontrolled illness * No poorly compliant patients PRIOR CONCURRENT THERAPY: * No prior chemotherapy or radiotherapy * No prior investigational anticancer agents * More than 4 weeks since prior major surgery * More than 1 week since prior minor surgery, fine-needle aspiration, or core needle biopsy * No concurrent major surgery except planned neck dissection * No concurrent routine colony-stimulating factor therapy * No other concurrent investigational agents * No other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 5 yrs after treatment | The time to disease progression is calculated from the date of treatment. Data for patients who remain disease progression free are censored as of date when the last follow-up information is obtained. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 5 years | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). A response will be determined by at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD |
Countries
United States
Participant flow
Recruitment details
Patients recruited from University Hospitals (Cleveland OH) and University of Pittsburgh (Pittsburgh PA) from September 2005 through September 2008.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab With Docetaxel and Radiation Therapy Radiation therapy will be delivered using standard once-daily fractionation, five days a week for 8 weeks. Bevacizumab is administered intravenously once on day 1 every two weeks during the course of radiation and up to one year following completion of radiation therapy, at which point bevacizumab will be discontinued.Patients meeting planned neck dissection criteria, will not receive bevacizumab therapy following completion of concurrent chemo-radiation therapy (for at least 8 weeks prior to surgery). Bevacizumab therapy will restart 4 weeks after planned neck dissection for nine months.Docetaxel is administered intravenously once per week only during the course of radiation. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Complicating Disease | 1 |
| Overall Study | Disease Progression | 2 |
| Overall Study | exceed maximum delay in treatment | 1 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bevacizumab With Docetaxel and Radiation Therapy |
|---|---|
| Age, Customized 40-49 years | 4 participants |
| Age, Customized 50-59 years | 16 participants |
| Age, Customized 60-69 years | 9 participants |
| Age, Customized 70-79 years | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 12 / 30 |
Outcome results
Primary
Time to Progression
The time to disease progression is calculated from the date of treatment. Data for patients who remain disease progression free are censored as of date when the last follow-up information is obtained.
Time frame: 5 yrs after treatment
Population: Patients who received at least one treatment on study
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bevacizumab With Docetaxel and Radiation Therapy | Time to Progression | 44.2 Months |
Secondary
Response Rate
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). A response will be determined by at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
Time frame: 5 years
Population: Patients with evaluable tumors at the end of the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab With Docetaxel and Radiation Therapy | Response Rate | Complete Response | 16 participants |
| Bevacizumab With Docetaxel and Radiation Therapy | Response Rate | Partial Response | 6 participants |
| Bevacizumab With Docetaxel and Radiation Therapy | Response Rate | Progressive Disease | 1 participants |
| Bevacizumab With Docetaxel and Radiation Therapy | Response Rate | Stable Disease | 3 participants |