Clinical trial NCT01634880: Postoperative Radiotherapy and Panitumumab in High-Risk Salivary Gland Malignancies
Official title: Phase II Trial of Postoperative Radiotherapy and Panitumumab in High-Risk Salivary Gland Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Salivary Gland Malignancy
Keywords: Salivary Gland Malignancies
Panitumumab
Postoperative
Radiotherapy
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
name: University of North Carolina, Chapel Hill
First posted: 2012-07-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.
* Pregnant or breast-feeding women are excluded (see 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Recurrence-free survival
timeFrame: 5-7 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5-7 years
measure: Efficacy
timeFrame: 5 years
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at UTHSCSA
state: Texas
Study officials:
affiliation: University of Texas Health Science Center San Antonio
name: Athanassios Argiris, MD
role: PRINCIPAL_INVESTIGATOR
References: