Angiogenic and EGFR Blockade With Curative Chemoradiation for Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

Concurrent Angiogenic and EGFR Blockade in Conjunction With Curative Intent Chemoradiation for Locally Advanced Head and Neck Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140556
• Other study ID #: Pro00008840
• Secondary ID: 7077
• Status: Completed
• Phase: Phase 0
• First received: August 29, 2005
• Last updated: January 14, 2013
• Start date: August 2005
• Est. completion date: April 2010

Study information

• Verified date: January 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Radiotherapy (RT) with concurrent chemotherapy represents the state of the art in curative intent treatment for locally advanced squamous carcinoma of the head and neck. Tumor hypoxia and high levels of angiogenesis (blood vessel formation) are associated with treatment failure. Preclinical models reveal that radiotherapy itself may induce tumor secretion of vascular endothelial growth factor (VEGF). Curability may consequently be reduced by multiple mechanisms. Over-expression of epidermal growth factor receptor (EGFR) also occurs commonly and increases the risk of treatment failure. The addition of EGFR blockade to RT alone increases the chance of a cure. Concurrent VEGF and EGFR blockade could be synergistic with one another and improve the effectiveness of concurrent chemoradiation for advanced head and neck cancer.

This study will add angiogenic and epidermal growth factor receptor (EGFR) blockade into an established program of curative intent concurrent chemoradiation for locally advanced head and neck cancer. The safety and effectiveness of delivering the drugs bevacizumab and Tarceva in conjunction with twice daily irradiation and concurrent cisplatin (CDDP) chemotherapy will be determined.

Description:

Pre Radiation Period:

• Bevacizumab (10 mg/kg) on days -14 and 0, or

• Tarceva (100 mg) daily from -14-0, or

• Bevacizumab (10 mg/kg) on days -14 and 0; Tarceva (100 mg) daily from -14-0

Chemoradiation Period:

• Radiotherapy may be delivered via conventional 2-D, conformal 3-D, or intensity modulated (IMRT) technique as is clinically indicated. Radiotherapy and CDDP doses will be delivered uniformly to all treatment cohorts:

• RT: 1.25 Gy BID M-F with a 6 hour interfraction interval

• Treatment break during week 4. Total dose 70 Gy/7 weeks

• CDDP: 33 mg/m2 M-W on weeks 1 and 5 of RT with standard DUMC hydration and anti-emetic regimens

• Bevacizumab (10mg/kg): Monday of weeks 1, 3, 5, 7 of RT

• Tarceva (100 mg): Daily for weeks 1-7 of treatment, except for days receiving CDDP

Safety Assessments:

• Baseline and then weekly assessments of blood pressure and urine protein : creatinine ratios during lead in and chemoRT phases of treatment

• Baseline carotid Doppler ultrasound evaluation

• Carotid Doppler ultrasound evaluation 1 month post-chemoRT

Efficacy Assessments:

• MR Imaging/Spectroscopy to be done at baseline, end of lead-in phase, end of week 1 of chemoRT, and end of chemoRT

• Angiogenic and EGFR related cytokines. Specifically, blood samples will be obtained to assay levels of VEGF, b-FGF, IL-8, D-dimer, EGF, TGF. These samples will be obtained on the same dates as the MR studies with an additional set of samples obtained at the midpoint of the lead in phase of treatment (day -7).

Clinical Assessments:

• All patients will undergo a minimum of once weekly interval history and physical examination including fiberoptic pharyngoscopy/laryngoscopy when indicated in the Department of Radiation Oncology to monitor for side effects and response to treatment as per standard routine for the care of patients with head and neck cancer.

• Patient compliance with Tarceva administration monitored via diary MRI/MRS (Magnetic Resonance Spectroscopy) DE-MRI

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2010
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally advanced squamous carcinoma of the head and neck (AJCC stages II/IV, M0, and excluding T1N1 and T1N2) undergoing curative intent concurrent chemoradiation.

• Previous treatment of any sort other than a biopsy is not allowed.

• Eligible anatomic sites:

• oral cavity

• oropharynx

• hypopharynx

• supraglottic

• glottic larynx

• KPS > 60

Exclusion Criteria:

• Nasopharynx primary

• History of malignancy other than basal cell skin cancer.

• History of claudication, bleeding, or thromboembolic disorders. Patients receiving heparin or Coumadin therapy are ineligible.

• Primary tumor or lymph node encasement of the carotid artery

• Blood pressure of >150/100 mmHg

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infarction within 6 months

• History of stroke within 6 months

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.

• Minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to Day 0

• Pregnant (positive pregnancy test) or lactating

• Urine protein : creatinine ratio = 1.0 at screening

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0

• Serious, non-healing wound, ulcer, or bone fracture

• AST, ALT, or bilirubin > 1.5 x normal

• PT or PTT > 1.5 x normal

• Platelets < 100,000

• WBC < 2000

• Hgb < 10

• Creatinine clearance < 60 mL/hr

• Refusal to provide written informed consent

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Pharynx Cancer

Intervention

Radiation:
• Chemoradiotherapy
External beam radiation daily (M-F)

Drug:
• Cisplatin
Cisplatin week 1 and 5 of radiation
• Bevacizumab
Bevacizumab (Avastin) day 1 of weeks 1, 3, and 5 of radiation
• Erlotinib
Erlotinib daily during radiation

Locations

Country	Name	City	State
United States	Department of Radiation Oncology; Duke University Medical Center	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
David M. Brizel, MD	Genentech, Inc., OSI Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (6)

Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998 Jun 18;338(25):1798-804. — View Citation

Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999 Nov;53(2):113-7. — View Citation

Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349-53. — View Citation

Craciunescu O, Brizel D, Cleland E, Yoo D, Muradyan N, Carroll M, Barboriak D, MacFall J. Dynamic contrast enhanced-MRI in head and neck cancer patients: variability of the precontrast longitudinal relaxation time (T10). Med Phys. 2010 Jun;37(6):2683-92. — View Citation

Dewhirst MW, Poulson JM, Yu D, Sanders L, Lora-Michiels M, Vujaskovic Z, Jones EL, Samulski TV, Powers BE, Brizel DM, Prosnitz LR, Charles HC. Relation between pO2, 31P magnetic resonance spectroscopy parameters and treatment outcome in patients with high-grade soft tissue sarcomas treated with thermoradiotherapy. Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):480-91. — View Citation

Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell. 2004 May;5(5):429-41. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Resolution	Complete response (resolution) of tumor on clinical exam.	Within 30 days of completing RT	No
Secondary	Local Regional Control		1 yr following chemoradiation	No
Secondary	Failure Free Survival		3 yrs	No

External Links

•   Medical Physics Study Publication Link