Bevacizumab, Docetaxel, and Radiation Therapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer

A Phase II Study of Bevacizumab in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Biological: bevacizumab; Drug: docetaxel; Procedure: conventional surgery; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake/University Ireland Cancer Center
    • Middleburgh Heights, Ohio, United States, 44130
      • Southwest General Health Center
    • Orange Villager, Ohio, United States, 44122
      • UHHS Chagrin Highlands Medical Center
    • Westlaker, Ohio, United States, 44145
      • UHHS Westlake Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: bevacizumab with docetaxel and radiation therapy

Biological: bevacizumab; 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.; Drug: docetaxel; docetaxel IV over 1 hour once a week for 8 weeks; Procedure: conventional surgery; 8-10 weeks after the completion of chemoradiotherapy, patients may undergo neck dissection; Radiation: radiation therapy; radiotherapy once daily, 5 days a week, for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 yrs after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Panayiotis Savvides, MD, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Publications and helpful links

General Publications

• Yao M, Galanopoulos N, Lavertu P, Fu P, Gibson M, Argiris A, Rezaee R, Zender C, Wasman J, Machtay M, Savvides P. Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck. Head Neck. 2015 Nov;37(11):1665-71. doi: 10.1002/hed.23813. Epub 2014 Oct 29.

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Estimate): June 9, 2015
• Last Update Submitted That Met QC Criteria: May 19, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: 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 oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx; 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
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Docetaxel; Bevacizumab
• Other Study ID Numbers: CASE6304 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); 03-05-50 (Other Identifier: University Hospitals IRB)