Neoplasms

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Head and Neck Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Bevacizumab

Cisplatin

Endothelial Growth Factors

Mitogens

Erlotinib Hydrochloride

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva

Chemoradiotherapy

Bevacizumab (Avastin) day 1 of weeks 1, 3, and 5 of radiation

Erlotinib

David M Brizel, MD

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.

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

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

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

Complete response (resolution) of tumor on clinical exam.

Genentech, Inc.

OSI Pharmaceuticals

David M. Brizel, MD

Professor, Radiation Oncology

Toxicity assessment weekly during treatment, and post treatment at 1 month and every 3 months through year 2.

Entire Study Population

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Feeding Tube Present Baseline

No Feeding Tube at Baseline

Feeding tube present before start of treatment

Feeding Tube

David Brizel, MD

2 participants had occult primaries, thus were not included in clinical complete response

Spots Global Cancer Trial Database for pharynx neoplasms