Clinical Trial: Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Johnny Kao

Current Primary Outcome: Toxicity [ Time Frame: 30 DAYS ]

Number of participants with acute and late toxicity


Original Primary Outcome: Acute toxicity [ Time Frame: 30 DAYS ]

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Locoregional Control, Progression-free Survival, Overall Survival and Late Toxicity [ Time Frame: 2 YEARS ]

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: September 1, 2009
Date Started: February 2007
Date Completion:
Last Updated: February 24, 2017
Last Verified: February 2017