Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer

NCT03021993 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 102510
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to look at the effectiveness of nivolumab in patients with oral cavity cancer (OCC) who are about to undergo surgery.

Conditions

Oral Cavity SCC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate Using Pathological Response

  Objective response rate: the sum of patients with either a pCR defined as no invasive and no in situ residuals present in the surgical specimen or partial pathologic response defined at least a 30% reduction in the size of the lesion in the surgical specimen. The reduction in size will be determined by comparing the pretreatment clinical measurements (the sum of the greatest axial measurement obtained with calipers at the time of initial evaluation) with the final pathologic measurements.

  Time of surgery (day 36 or day 50)

Secondary Outcomes (6)

• Level of Treg Cells in Peripheral Blood Using Immunostaining

  Day 1 and time of surgery (day 36 or day 50)

• Level of Activated T-cells in Peripheral Blood

  Day 1 and time of surgery (day 36 or day 50)

• Level of Immune Stimulatory Cytokines in Peripheral Blood

  Day 1 and time of surgery (day 36 or day 50)

• Expression of IFN-gamma in CD4+ Cells

  Day 1 and time of surgery (day 36 or day 50)

• Expression of Granzyme-B in CD8+ Cells From Peripheral Blood

  Day 1 and time of surgery (day 36 or day 50)

Study Arms (1)

Nivolumab

EXPERIMENTAL

Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab will be administered on days 1, 15 and 29. If disease has progressed at day 29, the subject will proceed to surgery. If a response or stable disease is present after the third dose, a fourth dose will be given on day 43, then the subject will proceed to surgery.

Also known as: OPDIVO

Nivolumab

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed histologically proven locoregional OCSCC without evidence of distant metastases and a clinically determined T-stage of 2-4,
• Recurrent or persistent histologically proven locoregional OCSCC that was initially treated with surgery alone, and a clinically determined recurrent T-stage of 2-4.
• Note - OCSCC includes the subsites of oral tongue, floor of mouth, gingiva, retromolar trigone, and buccal mucosa.
• Note - To allow sufficient tumor tissue for the immunological analyses, patients with T-stage 1 OCSCC will be excluded
• Greater than or equal to 18 years of age
• ECOG performance status of 0 or 1
• Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
• WBC \> 2,000/µL
• Absolute Neutrophil Count \>1,500/µL
• Platelets \> 100 X 103/µL
• Hemoglobin \> 9.0 g/dL
• Serum creatinine \< 1.5 X ULN or CrCl \> 40mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
• AST/ALT ≤ 3 x ULN
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)

You may not qualify if:

• Prior immunotherapy or treatment with another anti PD 1 agent
• Prior chemotherapy including Cetuximab or radiation therapy
• Previous severe hypersensitivity reaction to another monoclonal antibody
• Women who are pregnant, lactating or expecting to conceive
• Men who are expecting to father children within the research period
• Known history of HIV or AIDS
• Positive test for HBV sAg or HCV antibody indicating acute or chronic infection
• Concomitant malignancies except cutaneous squamous cell carcinoma or basal cell carcinoma
• Unresectable primary tumor or regional disease; presence of distant metastases.
• History of pneumonitis or interstitial lung disease
• Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Presence of condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or 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

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (2)

• Knochelmann HM, Horton JD, Liu S, Armeson K, Kaczmar JM, Wyatt MM, Richardson MS, Lomeli SH, Xiong Y, Graboyes EM, Lentsch EJ, Hornig JD, Skoner J, Stalcup S, Spampinato MV, Garrett-Mayer E, O'Quinn EC, Timmers CD, Romeo MJ, Wrangle JM, Young MRI, Rubinstein MP, Day TA, Lo RS, Paulos CM, Neskey DM. Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100426. doi: 10.1016/j.xcrm.2021.100426. eCollection 2021 Oct 19.

  PMID: 34755137 DERIVED

• Liu S, Knochelmann HM, Lomeli SH, Hong A, Richardson M, Yang Z, Lim RJ, Wang Y, Dumitras C, Krysan K, Timmers C, Romeo MJ, Krieg C, O'Quinn EC, Horton JD, Dubinett SM, Paulos CM, Neskey DM, Lo RS. Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100411. doi: 10.1016/j.xcrm.2021.100411. eCollection 2021 Oct 19.

  PMID: 34755131 DERIVED

Related Links

• Xiong et al. BMC Cancer (2020) 20:229
• Knochelmann et al., 2021, Cell Reports Medicine 2, 100426

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

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: Alan Brisendine, Sponsor-Investigator Support Unit Manager
• Organization: Medical University of South Carolina

brisend@musc.edu

843-792-9007

Study Officials

• David Neskey, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: January 16, 2017
• Study Start: May 30, 2017
• Primary Completion: November 15, 2021
• Study Completion: November 15, 2021
• Last Updated: November 12, 2025
• Results First Posted: November 12, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)