Postoperative Radiotherapy and Panitumumab in High-Risk Salivary Gland Malignancies

NCT ID: NCT01634880

Last Updated: 2016-05-23

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-03-31

Brief Summary

Standard therapy for high-risk or locally advanced salivary gland malignancies is surgery followed by postoperative radiation therapy. Studies have shown the superiority of combined modality therapy compared to surgery alone. Despite the addition of postoperative radiation therapy, the five-year survival for locally advanced salivary gland malignancies is poor (less than 60%). In salivary gland malignancies, the epidermal growth factor receptor (EGFR) is expressed in 25-85%; in certain histological types, like salivary duct carcinomas, the expression is higher. EGFR is a promising target of anticancer therapy. In squamous cell carcinoma of the head and neck, a phase III trial utilizing cetuximab added to radiation therapy improved both locoregional control and overall survival compared to radiation alone. Panitumumab is a novel, human, IgG2 EGFR monoclonal antibody that may be better tolerated and more efficacious than cetuximab. Here, the investigators hypothesize that the addition of panitumumab to standard radiotherapy in locally advanced salivary gland malignancies will improve recurrence-free survival (RFS).

Detailed Description

Specific Aims To determine the recurrence-free survival (primary endpoint), overall survival, local and distant recurrence-free survival, and treatment-related toxicities. Also, the investigators plan to study EGFR-related and immune biomarkers in baseline tumor tissue as well as blood samples obtained prior and after therapy.

Subject Population We will enroll patients with completely resected, locally advanced salivary gland cancers.

Treatment Plan Standard radiation 64-70Gy with 2.0 Gy daily fractions in 6-7 weeks. Panitumumab 2.5 mg/Kg IV, weekly during radiation (total of 6-7 doses).

Statistical Design and Sample Size Phase II, one-stage, study with the 3-year recurrence-free survival (RFS) as the primary endpoint. The sample size is 30 patients.

Conditions

Salivary Gland Malignancy

Study Design

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

Study Groups

Postoperative Radiotherapy and Panitumumab

Group Type: EXPERIMENTAL

Postoperative Radiotherapy and Panitumumab

Intervention Type: DRUG

The starting panitumumab dose is 2.5 mglkg given once a week. The total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose will be calculated based on the subject's actual weekly body weight.

Standard radiation 64-70Gy with 2.0 Gy daily fractions in 6-7 weeks. Panitumumab 2.5 mg/Kg IV, weekly during radiation (total of 6-7 doses).

Interventions

Postoperative Radiotherapy and Panitumumab

The starting panitumumab dose is 2.5 mglkg given once a week. The total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose will be calculated based on the subject's actual weekly body weight.

Standard radiation 64-70Gy with 2.0 Gy daily fractions in 6-7 weeks. Panitumumab 2.5 mg/Kg IV, weekly during radiation (total of 6-7 doses).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pathologically determined salivary gland cancer of the major or minor salivary glands of the head and neck (any histology) status post potentially curative surgical resection with no macroscopic residual disease. Patients should have AJCC 6th edition stage III with 1) extracapsular extension, 2) perineural invasion, 3) positive surgical margins or 4) high grade histology or stage IVA or IVB.
• No distant metastasis.
• No prior chemotherapy, biological-targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer.
• No more than 10 weeks (minimum of 3 weeks) should elapse between surgery and treatment on study.
• ECOG performance status of 0-2.
• Patients must have normal organ and marrow function.
• No prior invasive malignancy unless the disease-free survival is 3 years or more.
• Age 18+ years.

Exclusion Criteria

• Informed consent must be obtained from all patients prior to beginning research related treatment.
• Patients should have the ability to understand and the willingness to sign a written informed consent document.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months) uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction. All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study.
• Patients may not be receiving any other investigational agents.
• No history of prior malignancy, with the exception of basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival.
• Pregnant women are excluded from this study because chemotherapy and radiation therapy have the potential for teratogenic or abortifacient effects.
• All WOCBP must have a negative serum pregnancy test at baseline, or within 7 days prior to receiving investigational product. All WOCBP should be instructed to contact the Investigator if they suspect they might be pregnant.
• Prior severe infusion reaction to a human monoclonal antibody.

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

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Athanassios Argiris

OTHER

Sponsor Role: lead

Responsible Party

Athanassios Argiris

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Athanassios Argiris, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health Science Center San Antonio

Locations

Cancer Therapy and Research Center at UTHSCSA

San Antonio, Texas, United States

Countries

United States

Other Identifiers

HSC20120130H

Identifier Type: OTHER

Identifier Source: secondary_id

CTRC 11-37

Identifier Type: -

Identifier Source: org_study_id