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

This study has been terminated.
(Withdrawal of drug supply.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00720083
First received: July 19, 2008
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: vandetanib
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Disease-free Survival [ Time Frame: From randomization to date of failure (local, regional, or distant progression, or death) or last follow-up. Analysis occurs after 78 failures have been reported. ] [ Designated as safety issue: No ]
    This study terminated early with 34 subjects accrued out of 170 planned, therefore no analyses were performed.


Enrollment: 34
Study Start Date: November 2008
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: RT + Cisplatin
Patients undergo radiotherapy 5 times a week for up to 6.5 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: cisplatin
Given IV
Radiation: radiation therapy
Patients undergo radiotherapy 5 times a week for up to 6.5 weeks.
Experimental: RT + Cisplatin + Vandetanib
Patients undergo radiotherapy as in arm I and receive cisplatin IV over 1 hour once a week beginning on day 1 of radiotherapy. Patients also receive oral vandetanib once daily beginning 14 days prior to the start of radiotherapy. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: cisplatin
Given IV
Drug: vandetanib
Given orally
Radiation: radiation therapy
Patients undergo radiotherapy 5 times a week for up to 6.5 weeks.

Detailed Description:

OBJECTIVES:

Primary

  • To screen for an indication that the addition of vandetanib to chemoradiotherapy may prolong disease-free survival as compared to a combination of chemoradiotherapy in patients with resected, high-risk stage III or IV head and neck squamous cell carcinoma.

Secondary

  • To determine whether this treatment regimen can be delivered safely and successfully following surgical resection for advanced head and neck cancer.
  • To estimate the locoregional progression, distant metastasis, and overall survival rates for patients treated with this regimen.
  • To examine the distribution of selected biomarkers that may include but are not limited to EGFR (epidermal growth factor receptor, total and phosphorylated), E-cadherin, pMAPK (phosphorylated mitogen-activated protein kinase), pAKT, Stat-3 (signal transducer and activator of transcription 3), Ki-67, COX-2 (cyclooxygenase 2), and cyclin B1 (G2/mitotic-specific cyclin-B1)expression in this group of patients and to explore the potential correlation between these markers with the ultimate treatment outcome

OUTLINE: This is a multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1) and primary site of disease (oral cavity/hypopharynx vs larynx vs oropharynx, HPV+ (human papillomavirus positive) vs oropharynx, HPV- (human papillomavirus negative)). Patients are randomized to 1 of 2 arms.

  • Arm I: Patients undergo radiotherapy 5 times a week for up to 6.5 weeks and receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.
  • Arm II: Patients undergo radiotherapy as in arm I and receive cisplatin IV over 1 hour once a week beginning on day 1 of radiotherapy. Patients also receive oral vandetanib once daily beginning 14 days prior to the start of radiotherapy.

In both arms, treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity.

Tissue samples from all patients are collected and reviewed. Tissue from patients with oropharyngeal carcinoma is analyzed for human papillomavirus.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720083

  Show 63 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Principal Investigator: David Raben, MD University of Colorado, Denver
Study Chair: John A. Ridge, MD, PhD Fox Chase Cancer Center
Study Chair: Stuart J. Wong, MD Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00720083     History of Changes
Other Study ID Numbers: RTOG-0619, CDR0000599867
Study First Received: July 19, 2008
Results First Received: March 22, 2013
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
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

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014