Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer
Recruitment status was Recruiting
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.
Cancer of the Pharynx
Cancer of the Larynx
Cancer of the Neck
Paranasal Sinus Neoplasms
Cancer of the Head
Drug: erlotinib + celecoxib
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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|
- Acute toxicity [ Time Frame: 30 DAYS ] [ Designated as safety issue: Yes ]
- locoregional control, progression-free survival, overall survival and late toxicity [ Time Frame: 2 YEARS ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2007|
|Estimated Study Completion Date:||November 2010|
|Estimated Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
|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
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 cycloxygenase-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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00970502
|Contact: Johnny Kao, M.D.||212-241-7503||Johnny.firstname.lastname@example.org|
|Contact: Stuart Packer, M.D.||212-241-8617||stuart.packer@Mountsinai.org|
|United States, New York|
|Mount Sinai School of Medicine||Recruiting|
|New York, New York, United States, 10029|
|Contact: Johnny Kao, M.D 212-241-7503 Johnny.email@example.com|
|Contact: Stuart Packer, M.D 212-241-8617 stuart.packer@Mountsinai.org|
|Principal Investigator: Johnny Kao, M.D.|
|Sub-Investigator: Stuart Packer, M.D.|
|Principal Investigator:||Johnny Kao, M.D.||Mount Sinai School of Medicine|