A Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer
Overview
- Phase
- Phase 3
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Neck Squamous Cell Carcinoma of Unknown Primary
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 403
- Locations
- 1561
- Primary Endpoint
- Overall Survival (OS)
- Status
- Active, not recruiting
- Last Updated
- yesterday
Overview
Brief Summary
This randomized phase III trial studies chemotherapy to see how well it works with or without bevacizumab in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other parts of the body (metastatic). Drugs used in chemotherapy, such as docetaxel, cisplatin, carboplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also make tumor cells more sensitive to chemotherapy and stop the growth of head and neck cancer by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab in treating patients with head and neck squamous cell carcinoma.
Detailed Description
PRIMARY OBJECTIVES: I. To compare the overall survival of patients with recurrent or metastatic head and neck cancer treated with standard platinum-based chemotherapy with or without bevacizumab. SECONDARY OBJECTIVES: I. To assess toxicities with the addition of bevacizumab to each platinum-doublet (cisplatin/docetaxel, carboplatin/docetaxel, cisplatin/fluorouracil \[5-FU\], carboplatin/5-FU). II. To compare the objective response rates and the progression-free survival achieved with the above therapies. III. To collect blood samples before and after therapy for future correlative studies. IV. To collect tumor tissue samples available at baseline from prior diagnostic procedures for future correlative studies. OUTLINE: After the physician decides which chemotherapy doublet to use, patients are randomized to 1 of 2 treatment arms for that chemotherapy combination. ARM IA: Patients receive chemotherapy comprising docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IB: Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA. ARM IIA: Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIB: Patients receive bevacizumab as in arm IB and docetaxel and carboplatin as in Arm IIA. ARM IIIA: Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IIIB: Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA. ARM IVA: Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM IVB: Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed squamous cell cancer of the head and neck (SCCHN), from any primary site, including unknown primary cancers of the head and neck; patient must not have nasopharyngeal carcinoma of histologic types World Health Organization (WHO) 2 or 3 or squamous cell carcinoma that originated in the skin
- •Patients must have SCCHN that is either (a) recurrent, judged incurable by surgery or radiation or (b) metastatic; NOTE: Patients who refuse radical resection for recurrent disease are eligible; NOTE: A second primary squamous cell carcinoma of the head and neck is allowed if eligibility is based on a recurrent or metastatic first primary squamous cell carcinoma of the head and neck
- •No prior chemotherapy or biologic/molecular targeted therapy for recurrent or metastatic SCCHN
- •Patients may have received one regimen of induction, concomitant chemoradiotherapy and/or adjuvant chemotherapy as part of initial potential curative therapy but must not have received prior chemotherapy for recurrent or metastatic disease
- •A minimum of 4 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment; in addition patients must be progression-free for at least 4 months after completion of chemotherapy or chemoradiotherapy or radiation plus cetuximab given with a curative intent; (cetuximab therapy: 4 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment if part of concurrent regimen, 8 weeks if part of adjuvant regimen post radiation)
- •Patients having progression after 2 cycles of induction chemotherapy are not eligible for the study
- •No prior bevacizumab is allowed
- •A maximum of one prior radiotherapy regimen, curative or palliative, to the head and neck is allowed; if the radiation is combined with chemotherapy and/or cetuximab, a minimum of 4 months must elapse between the end of radiotherapy and registration; if the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration; a minimum of 3 weeks must elapse between prior radiation to other areas and registration
- •Patients must not be receiving any other investigational agent while on the study
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Exclusion Criteria
- Not provided
Arms & Interventions
Arm IB (docetaxel, cisplatin, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA.
Intervention: Laboratory Biomarker Analysis
Arm IIA (docetaxel, carboplatin)
Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Docetaxel
Arm IA (docetaxel, cisplatin)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm IA (docetaxel, cisplatin)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Docetaxel
Arm IA (docetaxel, cisplatin)
Patients receive docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm IIA (docetaxel, carboplatin)
Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Arm IB (docetaxel, cisplatin, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA.
Intervention: Bevacizumab
Arm IB (docetaxel, cisplatin, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA.
Intervention: Cisplatin
Arm IB (docetaxel, cisplatin, bevacizumab)
Patients receive bevacizumab IV over 30-90 minutes on day 1 and docetaxel and cisplatin as in Arm IA.
Intervention: Docetaxel
Arm IIA (docetaxel, carboplatin)
Patients receive docetaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm IIB (docetaxel, carboplatin, bevacizumab)
Patients receive bevacizumab as in Arm IB and docetaxel and carboplatin as in Arm IIA.
Intervention: Bevacizumab
Arm IIB (docetaxel, carboplatin, bevacizumab)
Patients receive bevacizumab as in Arm IB and docetaxel and carboplatin as in Arm IIA.
Intervention: Carboplatin
Arm IIB (docetaxel, carboplatin, bevacizumab)
Patients receive bevacizumab as in Arm IB and docetaxel and carboplatin as in Arm IIA.
Intervention: Docetaxel
Arm IIB (docetaxel, carboplatin, bevacizumab)
Patients receive bevacizumab as in Arm IB and docetaxel and carboplatin as in Arm IIA.
Intervention: Laboratory Biomarker Analysis
Arm IIIA (cisplatin, fluorouracil)
Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm IIIA (cisplatin, fluorouracil)
Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorouracil
Arm IIIA (cisplatin, fluorouracil)
Patients receive cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm IIIB (cisplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA.
Intervention: Bevacizumab
Arm IIIB (cisplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA.
Intervention: Cisplatin
Arm IIIB (cisplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA.
Intervention: Fluorouracil
Arm IIIB (cisplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and cisplatin and fluorouracil as in Arm IIIA.
Intervention: Laboratory Biomarker Analysis
Arm IVA (carboplatin, fluorouracil)
Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Arm IVA (carboplatin, fluorouracil)
Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorouracil
Arm IVA (carboplatin, fluorouracil)
Patients receive carboplatin IV over 30 minutes on day 1 and fluorouracil IV continuously on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm IVB (carboplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Intervention: Bevacizumab
Arm IVB (carboplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Intervention: Carboplatin
Arm IVB (carboplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Intervention: Fluorouracil
Arm IVB (carboplatin, fluorouracil, bevacizumab)
Patients receive bevacizumab as in Arm IB and carboplatin and fluorouracil as in Arm IVA.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: assessed every 3 months within 2 years from study entry, then every 6 months up to 5 years from study entry
Overall survival (OS) was defined as time from randomization to death from any course. Patients who were alive were censored at the last contact date. Median OS was estimated using the Kaplan-Meier method.
Secondary Outcomes
- Progression-free Survival (PFS)(on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks)
- Overall Response Rate(on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks)