Window Study of Nivolumab With or Without Ipilimumab in Squamous Cell Carcinoma of the Oral Cavity

NCT02919683 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-284
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for Squamous Cell Carcinoma of the oral cavity. The following drugs are involved in this study:

• Nivolumab (Opdivo™)
• Ipilimumab (Yervoy™)

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With a Volumetric Response Rate to Treatment

  Response rate to window treatment with single agent nivolumab or nivolumab combined with ipilimumab is determined using bidirectional measurements (product of longest 2 diameters of lesions) of primary and nodal lesions to be removed at the time of surgery. Responders will have demonstrated any reduction in overall tumor volume as determined by the product of the longest perpendicular bidirectional tumor measurements.

  At time of surgery

• Safety and Tolerability of Protocol Treatment

  Outcome measure includes number of participants with treatment-related adverse events as assessed by CTCAE v4.0, number of dose-limiting toxicities in safety run-ins following a 3 + 3 design, and delays to surgery.

  At the time of surgery

Secondary Outcomes (4)

• Percentage of Participants Demonstrating Objective Response Using RECIST Criteria

  At time of surgery

• Percentage of Participants Demonstrating Pathological Response

  At time of surgery

• Participant One Year Progression-Free Survival Percentage

  1 year

• Participant Overall Survival Percentage

  Data Cutoff (14.2 Months Median Follow Up)

Study Arms (2)

Nivolumab With Ipilimumab

EXPERIMENTAL

* Nivolumab to be delivered at a pre-determine dose for two weeks * Ipilimumab to be delivered at a pre-determine dose for one week * Blood Sample Collected * Standard of Care Surgery

Drug: Nivolumab; Drug: Ipilimumab; Procedure: Standard of Care Surgery

Nivolumab

EXPERIMENTAL

* Nivolumab to be delivered at a pre-determine dose for two weeks * Blood Sample Collected * Standard of Care Surgery

Drug: Nivolumab; Procedure: Standard of Care Surgery

Interventions

Nivolumab DRUG

Also known as: Opdivo

Nivolumab; Nivolumab With Ipilimumab

Ipilimumab DRUG

Also known as: Yervoy

Nivolumab With Ipilimumab

Standard of Care Surgery PROCEDURE

Nivolumab; Nivolumab With Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed squamous cell carcinoma of the oral cavity. Clinical stage \>=T2 (primary tumor greater than 2 cm in size) and/or evidence of regional nodal involvement by clinical exam or imaging
• Only patients 18 years and older are eligible. There is no upper age limit but the patients must be able to medically tolerate the regimen. Adverse event data are currently unavailable on the use immune checkpoint blockade for participants \< 18 years of age, and thus children are excluded from this study
• ECOG performance status \<=1
• Patients much be a surgical candidate (e.g. their disease must be considered resectable before any treatment and must have no serious medical contraindications that definitively preclude undergoing general anesthesia) Ability to understand and the willingness to sign a written informed consent document
• Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception (see Appendix B). WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. WOCBP is defined as any woman or adolescent who has begun menstruation and is not post- menopausal. A post-menopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
• Men who are sexually active with WOCBP must agree to use any contraceptive method (see Appendix B) with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception)
• Participants must have normal organ and marrow function as defined below:
• Laboratory parameters: WBC ≥ 2000/uL, Absolute neutrophil count (ANC) ≥ 1500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin (Hgb) ≥ 9 g/dL; Hgb-A1C ≤ 7.5%; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); Bilirubin ≤ 2.5 × ULN (≤ 4 × ULN for subjects with Gilbert's disease); Alkaline phosphatase ≤ 2.5 × ULN; Creatinine ≤ 1.5 × ULN

You may not qualify if:

• Pathologically proven, radiologic or clinical evidence of distant metastatic disease (this includes all disease below the clavicles, as well as disease metastatic to the bone, brain, or in the spinal canal)
• Any prior immunologic cancer therapy with systemic inhibitors of the PD-1 or CTLA-4 pathway
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; or if diagnosed and treated within the past 2 years for cervical cancer in situ or basal cell or squamous cell carcinoma of the skin
• Prior radiation to the head and neck region
• Prior chemotherapy within the last 2 years
• History of pneumonitis or interstitial lung disease
• Has evidence of active, noninfectious pneumonitis that required treatment with steroids.
• The subject is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA
• Lack of availability for follow up assessments
• Concurrent administration of other cancer specific therapy during the course of this study is not allowed
• Patients who require systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• The investigator's belief that the subject is medically unfit to receive nivolumab, and/or ipilimumab or unsuitable for any other reason

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Shah H, Wang Y, Cheng SC, Gunasti L, Chen YH, Lako A, Guenette J, Rodig S, Jo VY, Uppaluri R, Haddad R, Schoenfeld JD, Jacene HA. Use of Fluoro-[18F]-Deoxy-2-D-Glucose Positron Emission Tomography/Computed Tomography to Predict Immunotherapy Treatment Response in Patients With Squamous Cell Oral Cavity Cancers. JAMA Otolaryngol Head Neck Surg. 2022 Mar 1;148(3):268-276. doi: 10.1001/jamaoto.2021.4052.

  PMID: 35050348 DERIVED

• Schoenfeld JD, Hanna GJ, Jo VY, Rawal B, Chen YH, Catalano PS, Lako A, Ciantra Z, Weirather JL, Criscitiello S, Luoma A, Chau N, Lorch J, Kass JI, Annino D, Goguen L, Desai A, Ross B, Shah HJ, Jacene HA, Margalit DN, Tishler RB, Wucherpfennig KW, Rodig SJ, Uppaluri R, Haddad RI. Neoadjuvant Nivolumab or Nivolumab Plus Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1563-1570. doi: 10.1001/jamaoncol.2020.2955.

  PMID: 32852531 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jonathan Schoenfeld, M.D. M.P.H.
• Organization: Dana-Farber Cancer Institute

jonathan_schoenfeld@dfci.harvard.edu

617-632-3591

Study Officials

• Jonathan Schoenfeld, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 28, 2016
• First Posted: September 29, 2016
• Study Start: November 1, 2016
• Primary Completion: July 1, 2019
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 28, 2026
• Results First Posted: July 31, 2020

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)