Cisplatin, Bevacizumab, and Intensity-Modulated Radiation Therapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: bevacizumab; cisplatin; conventional surgery; intensity-modulated radiation therapy
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage II squamous cell carcinoma of the hypopharynx; 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; 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 paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity; tongue cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as cisplatin, 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 stop the growth of head
      and neck cancer by blocking blood flow to the tumor. Specialized radiation therapy that
      delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause
      less damage to normal tissue. Giving cisplatin and bevacizumab together with
      intensity-modulated radiation therapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving cisplatin and
      bevacizumab together with intensity-modulated radiation therapy works in treating patients
      with stage III or stage IV head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Stage III/IV HNSCC without distant metastasis, previously untreated. Patients with
             stage II squamous cell carcinoma of the hypopharynx will also be eligible.

          -  Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum
             creatinine > 1.5 mg/dL may be eligible if calculated creatinine clearance ≥ 55 ml/min
             by Cockcroft and Gault equation (or 24-hour urine collection).

          -  Age ≥ 18 years

          -  Karnofsky performance status ≥70%

          -  Adequate bone marrow function: absolute neutrophil count ≥ 1,500/μl, platelets ≥
             100,000/μl, hemoglobin ≥ 9 gm/dl

          -  Adequate hepatic function: Total bilirubin ≤ 1.5 X UNL (patients with Gilbert's
             syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X
             UNL), aspartate aminotransferase (AST) ≤ 2.5 X UNL, alanine aminotransferase (ALT) ≤
             2.5 X UNL, alkaline phosphatase ≤ 2.5 X UNL.

          -  Men and women of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

          -  Patients must have ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Prior chemotherapy or radiation therapy for HNSCC

          -  Prior treatment with bevacizumab or other agents specifically targeting VEGF

          -  Other active malignancy, other than indolent malignancies which the investigator
             determines are unlikely to interfere with treatment or efficacy analysis. For example,
             patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate
             cancer within the no current biochemical (PSA) or radiologic evidence of disease may
             enroll.

          -  Patients with nasopharyngeal carcinoma

          -  Patients who will receive amifostine as part of the radiation treatment plan

          -  Patients with skin breakdown/ulceration (CTCAE version 3.0, grade 2 or higher).

          -  Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in
             a clinical significant way with activities of daily living).

          -  Patients with multifocal peripheral sensory alterations or paresthesias (including
             tingling) interfering with function, per patient report (example: activities of daily
             living).

          -  History of arterial thromboembolic events, including transient ischemic attack (TIA),
             cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI) within
             the last 3 years.

          -  Urine protein: creatinine (UPC) ratio ≥ 1.0 at screening. A random urine sample is
             collected. Total protein (mg/dL) and spot creatinine (mg/dL) are ordered for this
             sample. The UPC ratio is calculated from the results of these tests.

          -  International normalized ratio (INR) > 1.5 or activated partial thromboplastin time
             (aPTT) > 1.5 X upper limits of normal (UNL),

          -  Current use of warfarin, current use of heparin or low-molecular weight heparin,
             chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal antiinflammatory
             medications known to inhibit platelet function. Treatment with dipyramidole
             (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and or cilostazol (Pletal) is
             not allowed.

          -  Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1
             teaspoon of more) within 1 month prior to Day 1 protocol treatment will be excluded
             from this trial. Patients with incidental blood mixed with phlegm are not excluded.

          -  Esophageal varices, non-healing ulcer, wound, or bone fracture are exclusion criteria.
             However, patients with skin breakdown overlying malignant neck lymphadenopathy may be
             eligible, at the discretion of the investigator.

          -  Anatomic lesion that increases the risk of serious hemorrhage, such as encasement or
             invasion of major blood vessels by primary tumor and/or by involved lymph nodes

          -  Blood pressure of > 150/100 mmHg

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure.

          -  Clinically significant peripheral vascular disease

          -  History of bleeding diathesis or hemorrhagic disorder, or coagulopathy.

          -  Major surgical procedure or significant traumatic injury within 28 days prior to
             treatment with bevacizumab

          -  Core biopsy within 15 days prior to treatment with bevacizumab.

          -  Minor surgical procedures such as fine needle aspirations or placement of percutaneous
             gastrostomy tube (PEG) less than 7 days prior to treatment with bevacizumab

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior enrollment.

          -  Inability to comply with study and/or follow-up procedures

          -  Women who are pregnant or lactating