Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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.

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

- Patients must have recovered to grade 1 or better from any acute effects of prior
surgery, chemotherapy, or radiation therapy, and should be > 4 weeks post surgery;
chronic late xerostomia, speech and swallowing abnormalities resulting from prior
radiation or surgery are permitted if nutritional status is stable

- Patients must have measurable disease based on Response Evaluation Criteria in Solid
Tumors (RECIST); baseline measurements and evaluations of all sites of disease must be
obtained =< 4 weeks prior to randomization; disease in previously irradiated sites is
considered measurable if there has been unequivocal disease progression or
biopsy-proven residual carcinoma following radiation therapy; persistent disease after
radiotherapy must be biopsy proven at least 8 weeks after completion of radiation
therapy; (radiographic findings are acceptable providing that clear-cut measurements
can be made)

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Hemoglobin (Hgb) >= 8.0 g/dL

- Platelet count >= 100,000/mm^3

- Creatinine clearance of >= 60 ml/min; creatinine clearance may be measured or
calculated; if calculating, creatinine clearance, use the Cockroft-Gault formula

- Total bilirubin within normal limits (must be obtained =< 2 weeks prior to
randomization)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the
range allowing for eligibility

- 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

- Alkaline phosphatase must be within the range allowing for eligibility

- Urine dipstick must be =< 0-1+ within 2 weeks (14 days) of randomization; if urine
dipstick result is > 1+, a calculation of urine protein creatinine (UPC) ratio is
required; patients must have a UPC ratio < 1.0 to participate in the study; NOTE: UPC
ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio
of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

- No known brain metastases

- Patients who meet the following criteria will be excluded:

- Tumors that invade major vessels (e.g. the carotid) as shown unequivocally by
imaging studies

- Central (i.e. within 2 cm from the hilum) lung metastases that are cavitary as
shown unequivocally by imaging studies

- Any prior history of bleeding related to the current head and neck cancer

- History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode
of coughing) =< 3 months prior to enrollment

- No history of coagulopathy or hemorrhagic disorders

- Patients should not have a history of thrombosis (e.g. pulmonary embolism or deep
venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use
of warfarin 1 mg per day is allowed) and international normalized ratio (INR) should
be < 1.5 at registration

- Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or
non-steroidal anti-inflammatory agents (NSAID's) known to inhibit platelet function;
the use of anti-platelet agents (e.g. dipyridamole [Persantine], ticlopidine [Ticlid],
clopidogrel [Plavix]) is allowed only if patient is not receiving aspirin or NSAID's
known to inhibit platelet function

- No hypercalcemia related to head and neck cancer

- Patients with a prior history of squamous cell or basal carcinoma of the skin or in
situ cervical cancer 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 3 years post diagnosis

- No current peripheral neuropathy >= grade 2 at time of randomization

- Patients must not have any co-existing condition that would preclude full compliance
with the study

- No prior history of severe hypersensitivity reaction to docetaxel or other drugs
formulated with polysorbate 80, if the physician's choice of chemotherapy regimen is
docetaxel

- All patients must have blood pressure =< 150/90 =< 2 weeks prior to randomization;
patients with history of hypertension must be well-controlled upon study entry (=<
150/90) on a stable regimen of anti-hypertensive therapy

- No major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to study enrollment, or anticipation of need for major surgical procedure
during the course of the study

- No unstable angina or myocardial infarction within the previous 6 months; no
symptomatic congestive heart failure, New York Heart Association (NYHA) grade II or
greater; 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 aortic dissection; no history of any central nervous system (CNS) cerebrovascular
ischemia or stroke within the last 6 months; no active serious infection

- Patients should not have prior 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

- Women must not be pregnant or breast feeding; pregnant women are excluded from this
study; women of child-bearing potential and men must agree to total abstinence or to
use adequate hormonal or barrier method of birth control prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while in this study, she should inform her treating physician immediately;
all females of childbearing potential must have a blood test or urine study within 2
weeks prior to randomization to rule out pregnancy

- Human immunodeficiency virus (HIV)-positive patients receiving combination
anti-retroviral therapy are excluded from the study; appropriate studies will be
undertaken in patients receiving combination anti-retroviral therapy when indicated

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to registration