Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
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This randomized phase III trial is studying chemotherapy to see how well it works with or without bevacizumab in treating patients with recurrent or metastatic head and neck cancer. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 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 cancer
Condition | Intervention | Phase |
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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Salivary Gland Cancer Recurrent Squamous Cell Carcinoma of the Hypopharynx Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Squamous Cell Carcinoma of the Oropharynx Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Recurrent Verrucous Carcinoma of the Larynx Recurrent Verrucous Carcinoma of the Oral Cavity Salivary Gland Squamous Cell Carcinoma Stage IV Salivary Gland Cancer Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Larynx Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IV Squamous Cell Carcinoma of the Oropharynx Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IV Verrucous Carcinoma of the Larynx Stage IV Verrucous Carcinoma of the Oral Cavity Tongue Cancer Untreated Metastatic Squamous Neck Cancer With Occult Primary |
Drug: docetaxel Drug: cisplatin Drug: fluorouracil Biological: bevacizumab |
Phase 3 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | A Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab In Patients With Recurrent Or Metastatic Head and Neck Cancer |
- Overall survival [ Time Frame: Time from randomization to date of death from any cause, censored at date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]Interim analyses comparing overall survival between the two arms using log-rank tests will be performed. The trial will be monitored according to principles of group-sequential methods using a one-sided O'Brien-Fleming upper boundary in order to preserve the overall type I error rate of 0.025. At each analysis, critical values for the log-rank test will be calculated using a truncated Lan-Demets error spending rate function corresponding to the O'Brien-Fleming boundary.
- Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: From course 1to up to 5 years ] [ Designated as safety issue: Yes ]The rates of grade 3-5 bleeding events will be monitored continuously and the difference between the treatment arms. A true rate of grade 5 bleeding events of 1-2% would be considered acceptable and is expected. One-sided Fisher's exact tests with alpha of 0.05 will be used at each interim analysis, and no adjustments will be made for multiple comparisons.
- Objective response rates [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The sum of the longest diameters of all target lesions will be calculated at baseline and reported as the baseline sum longest diameter. The sum longest diameter will be used to characterize the objective tumor response.
- Progression-free survival [ Time Frame: From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression, assessed up to 5 years ] [ Designated as safety issue: No ]
- Impact of comorbidities on endpoints [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Estimated Enrollment: | 400 |
Study Start Date: | August 2008 |
Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Active Comparator: Arm I (chemotherapy)
Patients receive chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1 OR cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously over days 1-4. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
|
Drug: docetaxel
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
Experimental: Arm II (chemotherapy, monoclonal antibody therapy)
Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with chemotherapy and bevacizumab repeats every 21 days in the absence of disease progression or unacceptable toxicity.
|
Drug: docetaxel
Given IV
Other Names:
Drug: cisplatin
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Biological: bevacizumab
Given IV
Other Names:
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To compare the overall survival of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with standard cisplatin-based chemotherapy with or without bevacizumab.
SECONDARY OBJEC TIVES:
I. To assess toxicities with the addition of bevacizumab to each cisplatin-doublet (cisplatin/docetaxel and cisplatin/fluorouracil).
II. To compare the objective response rates and the progression-free survival achieved with the above therapies.
OUTLINE: This is a multicenter study. Patients are stratified by performance status (0 vs 1), weight loss (< 5% vs ≥ 5% of total body weight in the past 6 months), prior radiotherapy to head and neck (yes vs no), and chemotherapy regimen (cisplatin/docetaxel vs cisplatin/fluorouracil). Patients are randomized to1 of 2 treatment arms.
ARM I (chemotherapy): Patients receive chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1-2 hours on day 1 OR cisplatin IV over 1-2 hours on day 1 and fluorouracil IV continuously over days 1-4. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity*.
ARM II (chemotherapy and bevacizumab): Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with chemotherapy and bevacizumab repeats every 21 days in the absence of disease progression or unacceptable toxicity*.
NOTE: *Treatment with chemotherapy may be discontinued if there is maximum response (i.e., no improvement in tumor measurements for 2 or more courses) after course 6; bevacizumab administration continues until disease progression in arm II.
After completion of study treatment, patients are followed every 3-6 months for 5 years.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (SCCHN) from any primary site, including unknown primary cancers of the head and neck
- No nasopharyngeal carcinoma of histologic types WHO 2 or 3
- No squamous cell carcinoma that originated in the skin
Recurrent disease, incurable disease as determined by surgery or radiation, or metastatic disease
- A second primary squamous cell carcinoma of the head and neck allowed if eligibility is based on a recurrent or metastatic first primary squamous cell carcinoma of the head and neck
- Patients who refuse radical resection for recurrent disease are eligible
Patients must have measurable disease based on RECIST
- Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma after radiotherapy
- Persistent disease after radiotherapy must be biopsy proven at least 8 weeks after completion of radiotherapy (radiographic findings are acceptable providing that clear cut measurements can be made)
Patients must be progression-free for at least 6 months after completion of chemotherapy or chemoradiotherapy or radiotherapy plus cetuximab given as part of initial potential curative therapy (if received such prior therapy)
- At least 6 months since completion of prior concurrent radiotherapy plus cetuximab (8 weeks for cetuximab given as part of adjuvant regimen post radiotherapy)
- Patients having progression after 2 courses of induction chemotherapy are not eligible
- No tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies (i.e., tumor crosses fat boundary)
- No central (i.e., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies
- No known brain metastases
- ECOG performance status 0-1
- ANC ≥ 1,500/mm^3
- Hemoglobin ≥ 8.0 g/dL
- Platelet count ≥ 100,000/mm^3
- Creatinine clearance ≥ 60 mL/min
- Total bilirubin normal
AST or ALT and alkaline phosphatase must meet one of the following criteria:
- Alkaline phosphatase normal AND AST or ALT ≤ 5 x upper limit of normal (ULN)
- Alkaline phosphatase > 1 but ≤ 2.5 x ULN AND AST or ALT > 1 but ≤ 1.5 x ULN
- Alkaline phosphatase > 2.5 but ≤ 5 x ULN AND AST or ALT normal
- Urine protein: creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Patients who meet the following criteria are excluded:
- Any prior history of bleeding related to the current head and neck cancer
- History of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) ≤ 3 months prior to enrollment
- No history of coagulopathy or hemorrhagic disorders
- No history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use of warfarin 1 mg/day is allowed)
- INR < 1.5 at registration
- No hypercalcemia related to head and neck cancer
Patients with a prior history of squamous cell or basal cell carcinoma of the skin or in situ carcinoma of the cervix must have been curatively treated
- Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease free for 5 years post diagnosis
- No current peripheral neuropathy ≥ grade 2
- Patients must not have any co-existing condition that would preclude full compliance with the study
- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 (if the physician's choice of chemotherapy is docetaxel)
Patients must have a blood pressure (BP) ≤ 150/90 within 2 weeks prior to randomization
- Patients with a history of hypertension must be well-controlled upon study entry (BP ≤ 150/90 mm Hg) on a stable regimen of anti-hypertensive therapy
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration
- No significant traumatic injury within the past 28 days
- No serious nonhealing wound, ulcer, or bone fracture
- No unstable angina or myocardial infarction within the past 6 months
- No symptomatic congestive heart failure or New York Heart Association (NYHA) class II-IV heart disease
- No history of aortic dissection or presence of aneurysm > 6 cm (or at high risk for rupture)
- No serious cardiac arrhythmia requiring medication (history of chronic atrial fibrillation or other atrial arrhythmia with controlled rate on medication is allowed)
- No clinically significant peripheral vascular disease manifested by intermittent claudication or need for vascular intervention
- No history of any CNS cerebrovascular ischemia or stroke within the past 6 months
- No active serious infection
- No history of a serious human anti-human antibody (HAHA)reaction
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
- Chronic latex xerostomia, speech and swallowing abnormalities, resulting from prior radiation or surgery, allowed provided nutritional status is stable
- No other prior malignancy except curatively treated squamous cell or basal carcinoma of the skin, in situ cervical cancer, or malignancy for which the patient has been curatively treated and remains disease-free for the past 3 years
- No concurrent bisphosphonates for bone metastasis unless initiated > 3 months before study entry
- Patients must have recovered to grade 1 or better from the effects of any prior surgery, chemotherapy, or radiotherapy AND >4 weeks post-surgery
No more than one prior radiotherapy regimen, curative or palliative, to the head and neck allowed
- At least 4 months since prior radiotherapy in combination with chemotherapy and/or cetuximab
- At least 8 weeks since prior radiotherapy given alone
- At least 3 weeks since prior radiotherapy to other areas
- No prior bevacizumab
No prior chemotherapy or biologic/molecular-targeted therapy for recurrent or metastatic SCCHN
Patients may have received one regimen of induction, concurrent chemoradiotherapy, and/or adjuvant chemotherapy as part of initial potential curative therapy
- A minimum of 6 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment
- No major surgical procedure or open biopsy within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study
- More than 4 weeks since prior surgery
- No other concurrent investigational agent
Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function
- The use of anti-platelet agents (e.g., dipyridamole [Persantine], ticlopidine [Ticlid], or clopidogrel [Plavix]) is allowed only if patient is not receiving aspirin or NSAIDs known to inhibit platelet function
- No HIV-positive patients on combination antiretroviral therapy
- No other concurrent chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiotherapy, or experimental medications
- No concurrent amifostine
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Principal Investigator: | Athanassios Argiris | Eastern Cooperative Oncology Group |
No publications provided
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00588770 History of Changes |
Other Study ID Numbers: | NCI-2009-00507, U10CA021115, CDR0000582533, E1305 |
Study First Received: | December 28, 2007 |
Last Updated: | September 20, 2012 |
Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Laryngeal Diseases Tongue Neoplasms Carcinoma, Verrucous Neoplasms, Unknown Primary Salivary Gland Neoplasms Hypopharyngeal Neoplasms Laryngeal Neoplasms Paranasal Sinus Neoplasms Oropharyngeal Neoplasms Nasopharyngeal Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type |
Neoplasms Neoplasms, Squamous Cell Neoplasms by Site Respiratory Tract Diseases Otorhinolaryngologic Diseases Mouth Neoplasms Mouth Diseases Stomatognathic Diseases Tongue Diseases Neoplasm Metastasis Neoplastic Processes Pathologic Processes Salivary Gland Diseases Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms |
ClinicalTrials.gov processed this record on October 17, 2012