Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer
Condition: Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma
Intervention: 3-Dimensional Conformal Radiation Therapy; Bevacizumab; Cisplatin; Fluorouracil; Intensity-Modulated Radiation Therapy
Intervention description: Undergo 3D-CRT; Given IV; Given IV; Given IV; Undergo IMRT
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Cisplatin; Fluorouracil; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with cisplatin,
      radiation therapy, and fluorouracil works in treating patients with stage IIB, stage III,
      stage IVA, or stage IVB nasopharyngeal cancer. 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 nasopharyngeal cancer by blocking blood flow to the
      tumor. Drugs used in chemotherapy, such as 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab
      together with chemotherapy and radiation therapy may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed cancer of the nasopharynx based on biopsy of a primary lesion
             and/or lymph nodes

               -  Histologic WHO types I-IIb/III

          -  Stage IIB-IVB disease

               -  No T1-2, N1 disease in which node positivity is based on the presence of
                  retropharyngeal lymph nodes

          -  No distant metastases

          -  Zubrod performance status 0-1

          -  WBC ? 4,000/mm?

          -  Hemoglobin ? 9.0 g/dL

          -  Platelet count ? 100,000/mm?

          -  Absolute neutrophil count ? 1,500/mm?

          -  INR ? 1.5

          -  aPTT ? 1.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase ? 1.5 times ULN

          -  ALT and AST ? 1.5 times ULN

          -  Bilirubin ? 1.5 times ULN

          -  Creatinine ? 1.5 mg/dL OR creatinine clearance ? 55 mL/min

          -  Urine protein:creatinine (UPC) ratio < 1.0

               -  If UPC > 0.5, 24-hour urine protein must be < 1,000 mg

          -  Hearing loss primarily sensorineural in nature and requiring a hearing aid or
             intervention that interferes in a clinically significant way with activities of daily
             living allowed

          -  Conductive hearing loss from tumor-related otitis media is allowed

          -  No severe, active comorbidity, including any of the following:

               -  Ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy within the past
                  6 months

               -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
                  within the past 6 months

               -  Esophageal varices, nonhealing wound, nonhealing ulcer, or bone fracture within
                  the past 6 months

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within the past 30 days

               -  Unstable angina and/or congestive heart failure or peripheral vascular disease
                  requiring hospitalization within the past 12 months

               -  Major medical or psychiatric illness that, in the opinion of the study
                  investigator, would preclude study compliance

               -  Active, untreated infection and/or acute bacterial or fungal infection requiring
                  intravenous antibiotics

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  History of significant weight loss (> 15% from baseline)

               -  History of arterial thromboembolic events

               -  Acquired immune deficiency syndrome

               -  Transmural myocardial infarction

               -  Cerebrovascular accident

               -  Transient ischemic attack

               -  Any other cardiac condition that, in the opinion of the investigator, would
                  preclude study compliance

          -  No gross hemoptysis or hematemesis, defined as bright red blood of ? 1 teaspoon per
             coughing episode, within the last 4 weeks (incidental blood mixed with phlegm allowed)

          -  No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or
             carcinoma in situ of the breast, oral cavity, or cervix

          -  Nutritional and physical condition considered suitable for study treatment

          -  No significant traumatic injury within the past 4 weeks

          -  No history of allergic reaction to the study drugs

          -  No baseline blood pressure > 150/100 mm Hg

          -  No peripheral neuropathy ? grade 2

          -  Not pregnant or nursing

          -  Negative serum pregnancy test

          -  Fertile patients must use effective contraception during and for ? 6 months after
             completion of study treatment

          -  At least 10 days since prior and no concurrent dipyridamole, ticlopidine, clopidogrel
             bisulfate, cilostazol, warfarin, heparin, daily treatment with acetylsalicylic acid (>
             325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet
             function

          -  No prior head and neck surgery of the primary tumor or lymph nodes except for
             incisional or excisional biopsies

               -  More than 15 days since prior biopsies

          -  More than 1 week since prior fine-needle aspirations or placement of percutaneous
             gastrostomy tube

          -  More than 4 weeks since prior major surgical procedures

          -  No prior radiotherapy to the region of the study cancer that would result in overlap
             of radiation therapy fields

          -  No prior bevacizumab or other vascular endothelial growth factor-targeting agents

          -  No prior systemic chemotherapy for the study cancer

               -  Prior chemotherapy for a different cancer allowed

          -  No concurrent hematologic growth factors (e.g. filgrastim [G-CSF], darbepoetin alfa,
             epoetin alfa) during study chemoradiotherapy

          -  No concurrent prophylactic growth factors for neutropenia during study adjuvant
             therapy

          -  No concurrent prophylactic amifostine or pilocarpine

          -  No other concurrent experimental therapeutic cancer treatments