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LarynxEarly Phase 1NCT03162731

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

A Early Phase 1 study testing Nivolumab, Ipilimumab and Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy in people with Larynx and Lip, Oral Cavity and Pharynx, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Larynx, Lip, Oral Cavity and Pharynx
What is being tested?
Nivolumab, Ipilimumab and Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
11 May 2017to 16 Nov 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic do not require contraception
  • Informed consent: all subjects must be able to comprehend and sign a written informed consent document

Who cannot join

  • 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
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  • 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
  • Patients must not be receiving any other investigational agents
  • Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial
  • Women must not be pregnant (as above) or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Pilot Trial of Nivolumab and Ipilimumab in Combination With Radiotherapy in Patients With Locally Advanced Head and Neck Cancer; CA209-931

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Nivolumab, Ipilimumab, Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy
Medical subject headings
Laryngeal Diseases, Lymphoid Interstitial Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called 946414-94-4, BMS-936558, MDX-1106, NIVO

    Given IV

  • IpilimumabBiological

    Also called 477202-00-9, 720801, 732442, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody

    Given IV

  • Simultaneous-Integrated Boost Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT-SIB, Intensity Modulated Radiation Therapy Simultaneous Integrated Boost, SIB-IMRT

    Undergo simultaneous integrated boost integrated modulated radiation therapy

  • Volume Modulated Arc TherapyRadiation

    Also called VMAT

    Undergo volumetric modulated arc therapy

Study groups in NCT03162731
Study groupRoleWhat they receive
Treatment ( nivolumab, ipilimumab, radiation therapy)ExperimentalPatients 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.
Receives: Biological: Nivolumab; Biological: Ipilimumab; Radiation: Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy; Radiation: Volume Modulated Arc Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2017
  2. Study start11 May 2017
  3. Primary completion27 Sep 2020
  4. Study completion16 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03162731
Sponsor's protocol ID
17P.082
Other IDs
JT 10025
Status last verified
Apr 2025
First submitted
19 May 2017
Last updated
29 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37536941

  • 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.

    PubMed 37019367

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Nivolumab, Ipilimumab and Simultaneous-Integrated Boost Intensity-Modulated Radiation Therapy in people with Larynx and Lip, Oral Cavity and Pharynx, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03162731, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.

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