Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Malignant Salivary Gland Tumors That Have Been Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with chemotherapy or alone after surgery in treating salivary gland tumors. PURPOSE: This randomized phase II/III trial is studying radiation therapy with or without chemotherapy to see how well it works in treating patients with high-risk malignant salivary gland tumors that have been removed by surgery.

Detailed Description
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OBJECTIVES: Primary Phase II Determine the feasibility of conducting a cooperative group prospective clinical trial in patients with resected malignant salivary gland tumors. Acquire preliminary efficacy data comparing postoperative radiotherapy alone to concurrent chemotherapy and radiation using weekly cisplatin. Phase III * Compare overall survival rates among patients receiving cisplatin and radiation to those receiving radiation alone. Secondary Phase II/III Compare the acute toxicities of these 2 adjuvant treatments. Compare late treatment-related adverse events in patients receiving postoperative radiation to those receiving concurrent chemoradiation. Compare progression-free survival rates among patients receiving cisplatin and radiation to those receiving radiation alone in both the cohort of patients with pathologically high-risk disease (high-grade adenocarcinoma, high-grade mucoepidermoid carcinoma, salivary duct carcinoma), and the patient cohort with pathologically intermediate-risk disease (all other eligible diagnoses). Investigate quality of life and patient-reported outcomes in patients enrolled in the study. Identify the histopathology and tumor marker expression from patients enrolled on this trial and assemble a tissue bank for future correlative studies. Establish a NRG Oncology baseline database for salivary gland malignancies to serve as a resource for future exploration of innovative and/or targeted approaches for this disease. OUTLINE: This is a multicenter study. Patients are stratified according to histology (high-grade mucoepidermoid carcinoma vs salivary duct carcinoma vs high-grade adenocarcinoma) and nodal status (N0 vs N1-3). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) 5 days a week for 6-6.5 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiotherapy. Arm II: Patients undergo 3D-CRT or IMRT as in Arm I. Tissue and blood samples may be collected for translational research studies. Patients may complete quality-of-life assessments periodically. After completion of study treatment, patients are followed up at 3, 6, 9, 12, and 24 months, every 6 months for 2 years, and then annually thereafter.

Official Title
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A Randomized Phase II/Phase III Study of Adjuvant Concurrent Radiation and Chemotherapy Versus Radiation Alone in Resected High-Risk Malignant Salivary Gland Tumors

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Radiation: 3-dimensional conformal radiation therapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically proven diagnosis of a malignant major salivary gland tumor or malignant minor salivary gland tumor of the head and neck of the following histologic subtypes: Intermediate-grade adenocarcinoma or intermediate-grade mucoepidermoid carcinoma High-grade acinic cell carcinoma or high-grade (>30% solid component) adenoid cystic carcinoma Surgical resection with curative intent within 8 weeks prior to registration All patients must have a Medical Oncology evaluation within 4 weeks prior to registration Pathologic stage T3-4 or N1-3 or T1-2, N0 with a close (≤ 1mm) or microscopically positive surgical margin; patients must be free of distant metastases based upon the following minimum diagnostic workup: History/physical examination within 8 weeks prior to registration Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to registration; at a minimum, contrast CT imaging of the chest is required (PET/CT is acceptable) No patients with residual macroscopic disease after surgery No prior systemic chemotherapy or radiation therapy for salivary gland malignancy PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Absolute neutrophil count (ANC) ≥ 1,800 cells/mm^3 Platelets ≥ 100,000 cells/mm^3 Hemoglobin ≥ 8.0 g/dL (the use of transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL is acceptable) Serum creatinine < 2.0 mg/dL Total bilirubin < 2 x the institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the institutional ULN Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment Not pregnant or nursing Patients must be deemed able to comply with the treatment plan and follow-up schedule Patients must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for central review No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) No severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (coagulation parameters are not required for entry into this protocol) Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition (HIV testing is not required for entry into this protocol) Protocol-specific requirements may also exclude immunocompromised patients Pre-existing ≥ grade 2 neuropathy No significant pre-existing hearing loss, as defined by the patient or treating physician PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior systemic chemotherapy or radiation therapy for salivary gland malignancy (prior chemotherapy for a different cancer is allowable) No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields No prior organ transplant No concurrent hematopoietic growth factors (e.g., G-CSF or pegfilgrastim) during radiotherapy No concurrent erythropoiesis-stimulating agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) 5 days a week for 6-6.5 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiotherapy. | Drug: cisplatin<br>* Given IV<br>Radiation: 3-dimensional conformal radiation therapy<br>* Undergo radiotherapy<br>Radiation: intensity-modulated radiation therapy<br>* Undergo radiotherapy<br>|
| Experimental: Arm II<br>Patients undergo 3D-CRT or IMRT as in arm I. | Radiation: 3-dimensional conformal radiation therapy<br>* Undergo radiotherapy<br>Radiation: intensity-modulated radiation therapy<br>* Undergo radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS), defined by the events of local-regional progression or recurrence, distant metastasis, or death from any cause, primarily at 2 years |  | From randomization to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) rate at 2 years |  | From randomization to 2 years. | 
| PFS rate at 5 years |  | From randomization to 5 years. | 
| OS rate at 5 years |  | From randomization to 5 years. | 
| Treatment-related toxicity, defined as any grade 3-4 adverse events (CTCAE v. 4) deemed to be definitely, probably, or possibly related to protocol treatment |  | From start of treatment to last follow-up. | 
| Treatment-related mortality, defined as any death during or within 30 days of discontinuation of protocol treatment |  | From start of treatment to 30 days after the end of treatment. | 
| Chemotherapy delivery as measured by percentage of protocol prescription given |  | From start of treatment to end of treatment. | 
| Radiation delivery as measured by elapsed treatment days |  | From start of treatment to end of treatment. | 
| Determine whether quality of life, fatigue and xerostomia differ as a function of treatment assignment at 3, 12, and 24 months after completing radiotherapy. |  | From randomization to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I salivary gland cancer, stage II salivary gland cancer, stage III salivary gland cancer, high-grade salivary gland mucoepidermoid carcinoma, salivary gland adenocarcinoma, stage IVA salivary gland cancer, stage IVB salivary gland cancer, stage IVC salivary gland cancer