Clinical trial NCT00720083: Chemotherapy and Radiation Therapy (RT) With or Without 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Cancer
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
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-07-22
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Disease-free Survival
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Altanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Anderson
country: United States
facility: Saint John's Cancer Center at Saint John's Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Commerce
country: United States
facility: Charach Cancer Center at Huron Valley - Sinai Hospital
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Kansas City
country: United States
facility: Truman Medical Center - Hospital Hill
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Lincoln
country: United States
facility: Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical Center
state: Nebraska
city: Reno
country: United States
facility: Renown Institute for Cancer at Renown Regional Medical Center
state: Nevada
city: Basking Ridge
country: United States
facility: Memorial Sloan-Kettering Cancer Center - Basking Ridge
state: New Jersey
city: Albuquerque
country: United States
facility: Radiation Oncology Associates, PA
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital of Rochester
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan-Kettering Cancer Center - Rockville Centre
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
state: New York
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center at ECU Medical School
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Mentor
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Furlong
country: United States
facility: Fox Chase Cancer Center Buckingham
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Cancer Institute at Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Wheeling
country: United States
facility: Schiffler Cancer Center at Wheeling Hospital
state: West Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
city: Oconomowoc
country: United States
facility: Regional Cancer Center at Oconomowoc Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Colorado, Denver
name: David Raben, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fox Chase Cancer Center
name: John A. Ridge, MD, PhD
role: STUDY_CHAIR
affiliation: Medical College of Wisconsin
name: Stuart J. Wong, MD
role: STUDY_CHAIR
References: