Chemotherapy and Radiation Therapy (RT) With or Without Vandetanib in Treating Patients With High-Risk Stage III or Stage IV Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: cisplatin; vandetanib; radiation therapy
Intervention description: Given IV; Given orally; Patients undergo radiotherapy 5 times a week for up to 6.5 weeks.
Intervention MeSH terms: Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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 verrucous carcinoma of the oral cavity; stage IV verrucous carcinoma of the oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx

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.
      Radiation therapy uses high-energy x-rays to kill tumor cells. Vandetanib may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known
      whether giving chemotherapy together with radiation therapy is more effective with or without
      vandetanib in treating patients with head and neck cancer.

      PURPOSE: This randomized phase II trial is studying giving chemotherapy together with
      radiation therapy to see how well it works compared with giving chemotherapy and radiation
      therapy together with vandetanib in treating patients with high-risk stage III or stage IV
      head and neck cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed squamous cell carcinoma of the head and
             neck, including any of the following subtypes:

               -  Oral cavity

               -  Oropharynx

               -  Larynx

               -  Hypopharynx

          -  Stage III or IV disease (no distant metastases)

          -  No cancer of the lip, nasopharynx, or sinuses

          -  Must have undergone gross total resection* (with curative intent) within 3-6 weeks of
             registration, with pathology demonstrating 1 or more of the following risk factors:

               -  Histologic extracapsular nodal extension

               -  Invasive cancer seen on microscopic evaluation of the resection margin, when all
                  visible tumor has been removed NOTE: *Tonsillar cancer patients who undergo
                  transoral excision of all gross tumor are eligible if the patient has formal neck
                  dissection confirming histologic extracapsular nodal extension

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  Zubrod performance status 0-1

          -  ANC (absolute neutrophil count) ≥ 2,000/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve this level
             allowed)

          -  Total bilirubin normal

          -  AST (aspartate aminotransferase) or ALT (alanine amino transferase) ≤ 2 times upper
             limit of normal (ULN)

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Serum creatinine ≤ 1.5 mg/dL

          -  Creatinine clearance ≥ 60 mL/min

          -  Glucose ≥ 40 mg/dL AND ≤ 250 mg/dL

          -  Sodium ≥ 130 mmol/L AND ≤ 155 mmol/L

          -  Magnesium ≥ 0.9 mg/dL AND ≤ 3 mg/dL (supplementation allowed)

          -  Potassium ≥ 4 mmol/L AND ≤ 6 mmol/L (supplementation allowed)

          -  Serum calcium (ionized or adjusted for albumin) ≥ 7 mg/dL AND ≤ 12.5 mg/dL
             (supplementation allowed)

          -  QTc (corrected QT interval) interval ≥ 480 msec must have 2 additional EKGs ≥ 24 hrs
             apart and the average QTc from the 3 screening EKGs must be < 480 msec

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for at least 60 days
             after completion of study treatment

          -  May not donate blood during the study or for 3 months after last dose of vandetanib

        Exclusion criteria:

          -  Other simultaneous primary cancer

          -  Prior invasive malignancy (except nonmelanoma skin cancer) unless disease free for a
             minimum of 3 years with the exception of the following:

               -  Carcinoma in situ of the cervix

               -  Adequately treated basal cell or squamous cell carcinoma of the skin

               -  Untreated or treated low-risk prostate cancer (defined as clinical or pathologic
                  T1c, N0 M0, PSA (prostate-specific antigen) < 10, Gleason < 7, < 50% of the total
                  cores positive for cancer)

          -  Severe, active co-morbidity, defined as follows:

               -  Clinically significant cardiovascular event (e.g., myocardial infarction,
                  superior vena cava syndrome, or New York Heart Association class II-IV) or
                  presence of cardiac disease that, in the opinion of the investigator, increases
                  the risk of ventricular arrhythmia within the past 3 months

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the past 3 months

               -  Transmural myocardial infarction within the past 3 months

               -  History of arrhythmia (e.g., multifocal premature ventricular contractions,
                  bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial
                  fibrillation) which is symptomatic or requires treatment (CTCAE [Common
                  Terminology Criteria for Adverse Events] grade 3), or asymptomatic sustained
                  ventricular tachycardia

                    -  Patients with atrial fibrillation, controlled on medication, are eligible

               -  Presence of left bundle branch block

               -  Previous history of QTc prolongation as a result from other medication that
                  required discontinuation of that medication

               -  Congenital long QTc syndrome or first degree relative with unexplained sudden
                  death under 40 years of age

               -  QTc with Bazett's correction that is unmeasurable or ≥ 480 msec on screening EKG

                    -  Patients who are receiving a drug that has a risk of QTc prolongation are
                       not eligible if QTc is ≥ 460 msec

               -  Hypertension (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm
                  Hg) not controlled by medical therapy

               -  Diarrhea ≥ grade 1 (increase of < 4 stools per day over baseline or mild increase
                  in ostomy output compared to baseline)

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within the past 30 days

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC (Center for
                  Disease Control) definition (no HIV testing is required for study entry)

          -  Prior allergic reaction to cisplatin or vandetanib or derivatives similar to these
             drugs

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior systemic chemotherapy for this disease (prior chemotherapy for a different
             cancer allowed)

          -  No prior radiotherapy to the head and neck area that would result in overlap of
             radiotherapy fields

          -  More than 30 days since prior investigational agents

          -  More than 3 weeks since prior major surgery and recovered

          -  More than 2 weeks since prior and no concurrent medications that induce Torsades de
             Pointes

          -  More than 2 weeks since prior and no concurrent known potent inducers of CYP3A4
             (Cytochrome P450 3A4), including rifampicin, phenytoin, carbamazepine, barbiturates,
             and Hypericum perforatum (St. John wort)

          -  No concurrent medication that may cause QTc prolongation