A Pilot Trial of Nivolumab and Ipilimumab in Combination With Radiotherapy in Patients With Locally Advanced Head and Neck Cancer; CA209-931
Overview
- Phase
- Early Phase 1
- Intervention
- Nivolumab
- Conditions
- Larynx
- Sponsor
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.03
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This pilot clinical trial studies the side effects of nivolumab, ipilimumab and radiation therapy in treating patients with stage IVA-B head and neck cancer. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may work better in treating patients with stage IVA-B head and neck cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To investigate the safety of the combination of nivolumab and ipilimumab with radiation treatment for definitive management of patients with locally advanced squamous cell carcinoma of the head and neck. SECONDARY OBJECTIVES: I. To estimate the 1 year progression-free survival (PFS) in all patients treated. II. To assess the overall response rate and overall survival of patients at one year TERTIARY OBJECTIVES: I. To explore whether PDL1 expression is associated with treatment response. II. To explore whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc) or cell subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc) within a patient's peripheral blood either at baseline or in response to treatment is associated with treatment response. III. To explore whether exosomes or other immune related serum biomarkers change after combination therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be 18 years of age and older
- •Pathologically confirmed squamous cell carcinoma of the head and neck (SCCHN), not previously treated
- •Stage III-IVB disease of 1) oral cavity, 2) HPV-negative (p16-) oropharynx, 3) larynx, 4) hypopharynx
- •Oropharyngeal primaries that are HPV-mediated (p16+) must be stage II-III. Stage II pateints must be either N2 or, if T3N0 or T3N1 they must also have at least 20 pack year history of smoking
- •Tumor sample must be available for HPV p16 and PD-L1 testing
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •White blood cells 2000/ul or more
- •Absolute neutrophil count 1500/ul or more
- •Platelets 100,000/ul or more
- •Hemoglobin 9 g/dl or more
Exclusion Criteria
- •Primary nasopharyngeal carcinoma
- •Patients with brain metastases
- •Patients who have participated in a study with an investigational agent or device within 2 weeks of initiation of treatment
- •Any prior radiotherapy to the neck
- •Patients with known contraindications to radiotherapy, including inherited syndromes associated with hypersensitivity to ionizing radiation (e.g., Ataxia-Telangiectasia, Nijmegen Breakage Syndrome)
- •Any prior chemotherapy or radiation therapy for the current diagnosis
- •Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- •Any history of a sever hypersensitivity reaction to any monoclonal antibody
- •Any history of allergy to the study drug components
- •Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post-diagnosis
Arms & Interventions
Treatment ( nivolumab, ipilimumab, radiation therapy)
Patients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Nivolumab
Treatment ( nivolumab, ipilimumab, radiation therapy)
Patients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Ipilimumab
Treatment ( nivolumab, ipilimumab, radiation therapy)
Patients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy
Treatment ( nivolumab, ipilimumab, radiation therapy)
Patients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Volume Modulated Arc Therapy
Outcomes
Primary Outcomes
Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.03
Time Frame: Up to 6 months
There will be continuous monitoring of the incidence of grade 3-5 toxicities.