Description:
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.
Title
- Brief Title: Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Malignant Salivary Gland Tumors That Have Been Removed By Surgery
- Official Title: A Randomized Phase II/Phase III Study of Adjuvant Concurrent Radiation and Chemotherapy Versus Radiation Alone in Resected High-Risk Malignant Salivary Gland Tumors
Clinical Trial IDs
- ORG STUDY ID:
RTOG-1008
- SECONDARY ID:
CDR0000686072
- SECONDARY ID:
NCI-2013-00370
- NCT ID:
NCT01220583
Conditions
Interventions
Drug | Synonyms | Arms |
---|
cisplatin | | Arm I |
Purpose
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
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm I | Experimental | 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 | Experimental | Patients undergo 3D-CRT or IMRT as in arm I. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Time Frame: | From randomization to 2 years. |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall survival (OS) rate at 2 years |
Time Frame: | From randomization to 2 years. |
Safety Issue: | |
Description: | |
Measure: | PFS rate at 5 years |
Time Frame: | From randomization to 5 years. |
Safety Issue: | |
Description: | |
Measure: | OS rate at 5 years |
Time Frame: | From randomization to 5 years. |
Safety Issue: | |
Description: | |
Measure: | 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 |
Time Frame: | From start of treatment to last follow-up. |
Safety Issue: | |
Description: | |
Measure: | Treatment-related mortality, defined as any death during or within 30 days of discontinuation of protocol treatment |
Time Frame: | From start of treatment to 30 days after the end of treatment. |
Safety Issue: | |
Description: | |
Measure: | Chemotherapy delivery as measured by percentage of protocol prescription given |
Time Frame: | From start of treatment to end of treatment. |
Safety Issue: | |
Description: | |
Measure: | Radiation delivery as measured by elapsed treatment days |
Time Frame: | From start of treatment to end of treatment. |
Safety Issue: | |
Description: | |
Measure: | Determine whether quality of life, fatigue and xerostomia differ as a function of treatment assignment at 3, 12, and 24 months after completing radiotherapy. |
Time Frame: | From randomization to 2 years. |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Radiation Therapy Oncology Group |
Trial Keywords
- 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
Last Updated
March 12, 2021