Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer

NCT ID: NCT00970502

Last Updated: 2017-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2010-11-30

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 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.

Conditions

Cancer of the Pharynx; Cancer of the Larynx; Cancer of the Neck; Paranasal Sinus Neoplasms; Cancer of the Head

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

erlotinib + celecoxib

Group Type: EXPERIMENTAL

erlotinib + celecoxib

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Tarceva; Celebrex

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnny Kao

OTHER

Sponsor Role: lead

Responsible Party

Johnny Kao

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Johnny Kao, M.D.

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai School of Medicine

New York, New York, United States

Countries

United States

References

Salama JK, Vokes EE, Chmura SJ, Milano MT, Kao J, Stenson KM, Witt ME, Haraf DJ. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):382-91. doi: 10.1016/j.ijrobp.2005.07.005. Epub 2005 Oct 5.

Reference Type: BACKGROUND

PMID: 16213104 (View on PubMed)

Kao J, Garofalo MC, Milano MT, Chmura SJ, Citron JR, Haraf DJ. Reirradiation of recurrent and second primary head and neck malignancies: a comprehensive review. Cancer Treat Rev. 2003 Feb;29(1):21-30. doi: 10.1016/s0305-7372(02)00096-8.

Reference Type: BACKGROUND

PMID: 12633577 (View on PubMed)

J. Kao, S. H. Packer, M. Teng, V. Gupta, K. Misiukiewicz, E. M. Genden; Mount Sinai School of Medicine, New York, NY, J Clin Oncol 28:15s, 2010 (suppl; abstr 5561).

Reference Type: BACKGROUND

Kao J, Genden EM, Chen CT, Rivera M, Tong CC, Misiukiewicz K, Gupta V, Gurudutt V, Teng M, Packer SH. Phase 1 trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer. Cancer. 2011 Jul 15;117(14):3173-81. doi: 10.1002/cncr.25786. Epub 2011 Jan 18.

Reference Type: RESULT

PMID: 21246519 (View on PubMed)

Other Identifiers

GCO 06-0509

Identifier Type: -

Identifier Source: org_study_id