Nivolumab, Ipilimumab, and Radiation Therapy in Treating Patients With Stage III-IVB Head and Neck Cancer

NCT03162731 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 17P.082JT 10025
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Larynx; Lip, Oral Cavity and Pharynx

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.03

  There will be continuous monitoring of the incidence of grade 3-5 toxicities.

  Up to 6 months

Study Arms (1)

Treatment ( nivolumab, ipilimumab, radiation therapy)

EXPERIMENTAL

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.

Biological: Nivolumab; Biological: Ipilimumab; Radiation: Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy; Radiation: Volume Modulated Arc Therapy

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: 946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment ( nivolumab, ipilimumab, radiation therapy)

Ipilimumab BIOLOGICAL

Given IV

Also known as: 477202-00-9, 720801, 732442, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment ( nivolumab, ipilimumab, radiation therapy)

Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy RADIATION

Undergo simultaneous integrated boost integrated modulated radiation therapy

Also known as: IMRT-SIB, Intensity Modulated Radiation Therapy Simultaneous Integrated Boost, SIB-IMRT

Treatment ( nivolumab, ipilimumab, radiation therapy)

Volume Modulated Arc Therapy RADIATION

Undergo volumetric modulated arc therapy

Also known as: VMAT

Treatment ( nivolumab, ipilimumab, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
• Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)
• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours of the start of study drugs
• Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level more than 40 mIU/mL

You may not qualify if:

• 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
• Any diagnosis of immunodeficiency or current immunosuppressive therapy including \>10mg/day of prednisone within 14 days of enrollment is not permitted
• Patients that have an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (\> 10 mg daily prednisone equivalents) or immunosuppressive agents; subjects with vitiligo, type I diabetes mellitus, or resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical steroids, and adrenal replacement steroids \</=10mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
• Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis
• Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
• Patients who have received a live vaccine within 30 days prior to the radiation therapy

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (2)

• Johnson JM, Vathiotis IA, Harshyne LA, Ali A, Bar Ad V, Axelrod R, Lorber E, Curry J, Cognetti DM, Luginbuhl AJ, Tuluc M, Keith S, Mahoney MG, Argiris A. Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. J Immunother Cancer. 2023 Aug;11(8):e007141. doi: 10.1136/jitc-2023-007141.

  PMID: 37536941 DERIVED

• Ali AS, Manukian G, Johnson JM, Vathiotis I, Axelrod R, Keith SW, Curry J, Cognetti D, Luginbuhl A, Argiris A, Bar-Ad V. In-Field Toxicity Analysis of a Phase 1 Clinical Trial of Nivolumab and Ipilimumab With Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck. Int J Radiat Oncol Biol Phys. 2023 Sep 1;117(1):181-185. doi: 10.1016/j.ijrobp.2023.03.065. Epub 2023 Apr 3. No abstract available.

  PMID: 37019367 DERIVED

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Laryngeal Diseases; Lymphoid Interstitial Pneumonia

Interventions

Nivolumab; Ipilimumab; CTLA-4 Antigen; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Jennifer Johnson, MD, PhD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: May 22, 2017
• Study Start: May 11, 2017
• Primary Completion: September 27, 2020
• Study Completion: November 16, 2022
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (1)