Oral Cavity SCCPhase 2NCT03021993
Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
A Phase 2 study testing Nivolumab in people with Oral Cavity SCC, run by Medical University of South Carolina at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Cavity SCC
- What is being tested?
- Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 30 May 2017to 15 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Newly diagnosed histologically proven locoregional OCSCC without evidence of distant metastases and a clinically determined T-stage of 2-4,
- OR
- 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
Show all 21Show fewer
- 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)
- Reproductive Status:
- WOCBP must use appropriate method(s) of contraception. 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.
- Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product.
- WOCBP 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 consecutive months of amenorrhea in a woman over 45.
- Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men, are not required to use contraception.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
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.
Read the detailed description
OCC patients who are scheduled for surgery will be given Nivolumab prior to surgery to see if there are any changes in surgical outcomes.
- Conditions
- Oral Cavity SCC
- Being tested
- Nivolumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
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.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time of surgery (day 36 or day 50)
Secondary outcomes (6)
Level of Treg Cells in Peripheral Blood Using Immunostaining
- Levels of Treg cells in pre and post treatment peripheral blood will be evaluated using immunostaining for CD4 and flow cytometric analysis of Foxp3. Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
Measured: Day 1 and time of surgery (day 36 or day 50)
Level of Activated T-cells in Peripheral Blood
- Levels of activated T-cells in peripheral blood will be assessed using flow cytometry for expression of CD69, IFN γ, T-bet and ICOS in CD4+ cells. Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
Measured: Day 1 and time of surgery (day 36 or day 50)
Level of Immune Stimulatory Cytokines in Peripheral Blood
- Intratumoral immune activity assessed by levels of immune stimulatory cytokines including IL-2, IFN γ, and IL-12 or inhibitory cytokine, IL10 and TGF-beta, in OCSCC tumor lysates will be measured flow cytometrically by cytokine bead array. Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
Measured: Day 1 and time of surgery (day 36 or day 50)
Expression of IFN-gamma in CD4+ Cells
Expression of interferon-gamma in CD4+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
Measured: Day 1 and time of surgery (day 36 or day 50)
Expression of Granzyme-B in CD8+ Cells From Peripheral Blood
Expression of Granzyme-B in CD8+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
Measured: Day 1 and time of surgery (day 36 or day 50)
Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood
- Expression of CD8+ cells expressing granzyme B (cytolytic response) from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
Measured: Day 1 and time of surgery (day 36 or day 50)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study start30 May 2017
- Primary completion15 Nov 2021
- Study completion15 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oral Cavity SCCStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- David Neskey, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021993
- Sponsor's protocol ID
- 102510
- Status last verified
- Oct 2025
- First submitted
- 20 Dec 2016
- Last updated
- 12 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34755137Liu 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.
PubMed 34755131
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
- ClinicalTrials.gov ID
- NCT03021993
- Acronym / sponsor ID
- 102510
- Conditions
- Oral Cavity SCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 30 May 2017 (actual)
- Primary completion
- 15 Nov 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Posted 12 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OCC patients who are scheduled for surgery will be given Nivolumab prior to surgery to see if there are any changes in surgical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: NivolumabNivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Newly diagnosed histologically proven locoregional OCSCC without evidence of distant metastases and a clinically determined T-stage of 2-4,
- OR
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OPDIVONivolumab 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. | Drug | Nivolumab |
Primary outcome
Objective Response Rate Using Pathological Response
Time frame: Time of surgery (day 36 or day 50)
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.
6 secondary outcomes
Level of Treg Cells in Peripheral Blood Using Immunostaining
Time frame: Day 1 and time of surgery (day 36 or day 50)
Level of Activated T-cells in Peripheral Blood
Time frame: Day 1 and time of surgery (day 36 or day 50)
Level of Immune Stimulatory Cytokines in Peripheral Blood
Time frame: Day 1 and time of surgery (day 36 or day 50)
Expression of IFN-gamma in CD4+ Cells
Time frame: Day 1 and time of surgery (day 36 or day 50)
Expression of Granzyme-B in CD8+ Cells From Peripheral Blood
Time frame: Day 1 and time of surgery (day 36 or day 50)
Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood
Time frame: Day 1 and time of surgery (day 36 or day 50)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34755137Knochelmann 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.
- Derived from this study: PubMed 34755131Liu 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.
- Xiong et al. BMC Cancer (2020) 20:229Link provided by the sponsor.
- Knochelmann et al., 2021, Cell Reports Medicine 2, 100426Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Oral Cavity SCC
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingObservational study
Head and Neck Carcinoma Clinical Research Platform for Molecular and Blood-based Biomarkers, Treatment and Outcome
Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx
RecruitingObservational study
Salivary IL-8 and Serum IL-6 as Biomarkers for Oral Potentially Malignant Disorders in Smokers and Never-Smokers
Oral Potentially Malignant Disorders, Oral Lichen Planus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Neskey, MD principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab in people with Oral Cavity SCC, run by Medical University of South Carolina 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 21 inclusion and 12 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 12 Nov 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate Using Pathological Response (time frame: Time of surgery (day 36 or day 50)). 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 NCT03021993, 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 12 Nov 2025.