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Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnny Kao, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT00970502
First received: September 1, 2009
Last updated: February 24, 2017
Last verified: February 2017
  Purpose
There is no optimal treatment for patients with recurrent head and neck cancer after previous radiation. Chemotherapy alone is not curative and patients survive an average of only 6 to 10 months. Surgery is not always possible and often cannot remove every cancerous cell. On the other hand, reirradiation with chemotherapy cures approximately 25 to 30% of patients but has significant toxicity with as many as 15 to 20% suffering from life-threatening or fatal complications. Therefore, less toxic and more effective reirradiation regimens are urgently needed. There are extensive data from animal studies and preliminary human studies showing that blocking epidermal growth factor receptor (EGFR) and COX-2 enhances radiation effect and is more effective than either treatment alone. Erlotinib is a FDA approved oral inhibitor of EGFR and celecoxib is a FDA approved COX-2 inhibitor. Both have been well studied in humans and appear to have less severe toxicity than conventional chemotherapeutic agents.

Condition Intervention Phase
Cancer of the Pharynx Cancer of the Larynx Cancer of the Neck Paranasal Sinus Neoplasms Cancer of the Head Drug: erlotinib + celecoxib Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase I/II Dose Escalation Trial of Induction and Concomitant Erlotinib and Celecoxib With Radiation Therapy for Treatment of Poor Prognosis Head and Neck Cancer, Including Reirradiation

Resource links provided by NLM:


Further study details as provided by Johnny Kao, Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 30 DAYS ]
    Number of participants with acute and late toxicity


Secondary Outcome Measures:
  • Clinical Response [ Time Frame: 20 months ]
    Response to Concurrent Erlotinib, Celecoxib, and Reirradiation according to Response Evaluation Criteria in Solid Tumors - Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

  • Locoregional Progression [ Time Frame: 20 months ]
    Patients with locoregional and/or distant progression

  • Locoregional Control, Progression-free Survival, Overall Survival and Late Toxicity [ Time Frame: 1 year ]
    At a median follow-up of 11 months, the 1 year locoregional control, progression-free survival, and overall survival rates.


Enrollment: 15
Study Start Date: February 2007
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: erlotinib + celecoxib Drug: erlotinib + celecoxib
In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression
Other Names:
  • Tarceva
  • Celebrex

Detailed Description:

Despite advances in the treatment of head and neck cancer, locoregional recurrences are the predominant site of treatment failure and are frequently the cause of death. Second primary tumors in the head and neck occur in up to 30% of patients at 10 years of follow-up after eradication of the original tumor due to field cancerization. The standard approach to patients with recurrent but non-metastatic disease has been surgical salvage alone. Unfortunately, this strategy is feasible in only a select group of patients and 5 year survival rates have ranged from 15-40%.

Most patients with previously irradiated unresectable recurrent or metastatic head and neck cancer are treated with chemotherapy alone. This approach has offered limited palliation with response rates of 10-40%, median survival of 5 to 10 months. While this may be an acceptable option for patients with clearly incurable widespread metastatic disease, it may not be the best approach for those patients with potentially curable locoregional disease.

While geographic misses and second primary tumors occur, the majority of patients have radioresistant tumors. Therefore, reirradiation alone is unlikely to be effective. High dose reirradiation with concomitant chemotherapy represents a more aggressive approach resulted in encouraging 3-year survival rates of 15 to 35%. This approach represents a potentially curative option for patients with unresectable or partially resected disease arising in a previously irradiated volume. However, the high rates of acute and late toxicity with this approach have limited widespread application of this approach.

Extensive preclinical and clinical data suggest that both epidermal growth factor receptor (EGFR) antagonists and cyclooxygenase-2 (COX-2) inhibitors enhance the effectiveness of ionizing radiation. In locally advanced head and neck cancer, a recent phase III trial concurrent anti-EGFR monoclonal antibody and radiation demonstrated improved local control, disease free survival and overall survival compared to radiation alone without the increased mucosal toxicity associated with concurrent chemotherapy. COX-2 inhibition and anti-EGFR therapy demonstrates activity against recurrent/metastatic head and neck cancer in a recent phase I study. Head and neck cancer represents an ideal site to study biologic markers of tumor response because of the accessibility of tumors for biopsy. Therefore, we propose the combination of Erlotinib and Celecoxib with radiation in a cohort of previously irradiation patients with head and neck cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck or lymphoepithelioma
  • Prior radiation to the head and neck, surgery or chemotherapy is allowed
  • Karnofsky performance status of >= 70%
  • Intact organ and bone marrow function
  • Obtained informed consent

Exclusion Criteria:

  • Demonstration of metastatic disease (i.e. M1 disease).
  • Incomplete healing from previous surgery
  • Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician.
  • Uncontrolled active infection unless curable with treatment of their cancer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970502

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Sponsors and Collaborators
Johnny Kao
Investigators
Principal Investigator: Johnny Kao, M.D. Icahn School of Medicine at Mount Sinai
  More Information

Publications:
Responsible Party: Johnny Kao, Assistant Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT00970502     History of Changes
Other Study ID Numbers: GCO 06-0509
Study First Received: September 1, 2009
Results First Received: December 23, 2016
Last Updated: February 24, 2017

Keywords provided by Johnny Kao, Icahn School of Medicine at Mount Sinai:
celecoxib
erlotinib
epidermal growth factor receptor
intensity-modulated radiotherapy
cyclooxygenase-2
reirradiation

Additional relevant MeSH terms:
Head and Neck Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Pharyngeal Neoplasms
Neoplasms by Site
Neoplasms
Otorhinolaryngologic Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Nose Neoplasms
Nose Diseases
Paranasal Sinus Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Erlotinib Hydrochloride
Celecoxib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2017