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

NCT00140556 | Completed Early Phase 1 Results

• 2 other identifiers: Pro000088407077
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Cancer; Pharynx Cancer

Keywords

head and neck cancer; targeted therapy; bevacizumab; erlotinib; Tarceva; radiotherapy; concurrent chemotherapy; pharynx cancer; tonsil cancer; hyperfractionation; angiogenesis; epidermal growth factor; vascular endothelial growth factor; magnetic resonance spectroscopy; cancer of the head and neck; upper aerodigestive tract neoplasms; pharynx neoplasms

Outcome Measures

Primary Outcomes (1)

• Tumor Resolution

  Complete response (resolution) of tumor on clinical exam.

  Within 30 days of completing RT

Secondary Outcomes (2)

• Local Regional Control

  1 yr following chemoradiation

• Failure Free Survival

  3 yrs

Study Arms (1)

ChemoRadiotherapy

EXPERIMENTAL

Radiation Therapy concurrent with cisplatin chemotherapy, Avastin and Tarceva

Radiation: Chemoradiotherapy; Drug: Cisplatin; Drug: Bevacizumab; Drug: Erlotinib

Interventions

Chemoradiotherapy RADIATION

External beam radiation daily (M-F)

ChemoRadiotherapy

Cisplatin DRUG

Cisplatin week 1 and 5 of radiation

ChemoRadiotherapy

Bevacizumab DRUG

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

Also known as: Avastin

ChemoRadiotherapy

Erlotinib DRUG

Erlotinib daily during radiation

Also known as: Tarceva

ChemoRadiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David M. Brizel, MD: lead
• Genentech, Inc.: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (1)

Department of Radiation Oncology; Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (8)

• 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. doi: 10.1016/s0167-8140(99)00102-4.

  PMID: 10665787 BACKGROUND

• 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. doi: 10.1056/NEJM199806183382503.

  PMID: 9632446 BACKGROUND

• 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. doi: 10.1016/s0360-3016(01)01630-3.

  PMID: 11567808 BACKGROUND

• 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. doi: 10.1016/j.ijrobp.2004.06.211.

  PMID: 15667971 BACKGROUND

• 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. doi: 10.1016/s1535-6108(04)00115-1.

  PMID: 15144951 BACKGROUND

• 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. doi: 10.1118/1.3427487.

  PMID: 20632579 RESULT

• Yoo DS, Kirkpatrick JP, Craciunescu O, Broadwater G, Peterson BL, Carroll MD, Clough R, MacFall JR, Hoang J, Scher RL, Esclamado RM, Dunphy FR, Ready NE, Brizel DM. Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer. Clin Cancer Res. 2012 Mar 1;18(5):1404-14. doi: 10.1158/1078-0432.CCR-11-1982. Epub 2012 Jan 17.

  PMID: 22253412 DERIVED

• Craciunescu OI, Yoo DS, Cleland E, Muradyan N, Carroll MD, MacFall JR, Barboriak DP, Brizel DM. Dynamic contrast-enhanced MRI in head-and-neck cancer: the impact of region of interest selection on the intra- and interpatient variability of pharmacokinetic parameters. Int J Radiat Oncol Biol Phys. 2012 Mar 1;82(3):e345-50. doi: 10.1016/j.ijrobp.2011.05.059. Epub 2011 Oct 8.

  PMID: 21985945 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Pharyngeal Neoplasms; Tonsillar Neoplasms

Interventions

Chemoradiotherapy; Cisplatin; Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Brizel, MD
• Organization: Duke University Medical Center, Dept Radiation Oncology

david.brizel@duke.edu

919 668-5637

Study Officials

• David M Brizel, MD

  Department of Radiation Oncology; Duke University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Radiation Oncology

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: September 1, 2005
• Study Start: August 1, 2005
• Primary Completion: May 1, 2009
• Study Completion: April 1, 2010
• Last Updated: January 18, 2013
• Results First Posted: August 31, 2011

Record last verified: 2013-01

Locations

US (1)