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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00720083
• Other study ID #: RTOG-0619
• Secondary ID: CDR0000599867
• Status: Terminated
• Phase: Phase 2
• First received: July 19, 2008
• Last updated: November 14, 2015
• Start date: November 2008
• Est. completion date: August 2011

Study information

• Verified date: November 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin
Given IV
• vandetanib
Given orally

Radiation:
• radiation therapy
Patients undergo radiotherapy 5 times a week for up to 6.5 weeks.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	This study terminated early with 34 subjects accrued out of 170 planned, therefore no analyses were performed.	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.	No