Chemotherapy and Radiation Therapy (RT) With or Without Vandetanib in Treating Patients With High-Risk Stage III or Stage IV Head and Neck Cancer

Not Recruiting

Trial ID: NCT00720083


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.

Official Title

A Randomized Phase II Trial of Chemoradiotherapy Versus Chemoradiotherapy and Vandetanib for High-Risk Postoperative Advanced Squamous Cell Carcinoma of the Head and Neck

Stanford Investigator(s)

Quynh-Thu Le, MD
Quynh-Thu Le, MD

Katharine Dexter McCormick and Stanley McCormick Memorial Professor and Professor, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS)



   - 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


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

   - 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


   - 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

   - 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


radiation: radiation therapy

drug: cisplatin

drug: vandetanib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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