Trial Outcomes & Findings for Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer (NCT NCT03021993)
NCT ID: NCT03021993
Last Updated: 2025-11-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Time of surgery (day 36 or day 50)
Results posted on
2025-11-12
Participant Flow
Participant milestones
| Measure |
Nivolumab
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Nivolumab
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
enrolled but were not treated
|
1
|
|
Overall Study
Death
|
3
|
Baseline Characteristics
Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Baseline characteristics by cohort
| Measure |
Nivolumab
n=17 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Age, Continuous
|
62.6 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
17 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Nivolumab
n=12 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Objective Response Rate Using Pathological Response
|
4 Participants
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
1\. 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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Level of Treg Cells in Peripheral Blood Using Immunostaining
Pre-treatment
|
7.7 percentage of treg cells
Standard Deviation 8.4
|
|
Level of Treg Cells in Peripheral Blood Using Immunostaining
Post-treatment
|
9.2 percentage of treg cells
Standard Deviation 9.1
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
2\. 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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Level of Activated T-cells in Peripheral Blood
Pre-treatment
|
58 percentage of CD8 IFN gamma T-cells
Standard Deviation 0.49
|
|
Level of Activated T-cells in Peripheral Blood
Post-treatment
|
62.2 percentage of CD8 IFN gamma T-cells
Standard Deviation 0.48
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
3\. 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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Level of Immune Stimulatory Cytokines in Peripheral Blood
Pre-treatment
|
26.4 percentage of cytokines
Standard Deviation 0.19
|
|
Level of Immune Stimulatory Cytokines in Peripheral Blood
Post-treatment
|
36.7 percentage of cytokines
Standard Deviation 0.48
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Expression of IFN-gamma in CD4+ Cells
Pre-treatment
|
20 percentage of CD4 positive cells
Standard Deviation 12.6
|
|
Expression of IFN-gamma in CD4+ Cells
Post-treatment
|
23.9 percentage of CD4 positive cells
Standard Deviation 13.5
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Expression of Granzyme-B in CD8+ Cells From Peripheral Blood
Pre-treatment
|
46.7 percentage of CD8 positive cells
Standard Deviation 15.8
|
|
Expression of Granzyme-B in CD8+ Cells From Peripheral Blood
Post-treatment
|
55.5 percentage of CD8 positive cells
Standard Deviation 15.7
|
SECONDARY outcome
Timeframe: Day 1 and time of surgery (day 36 or day 50)Population: Analysis includes 10 participants with complete pre- and post-treatment samples.
2\. 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.
Outcome measures
| Measure |
Nivolumab
n=10 Participants
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood
Post-treatment
|
42.6 percentage of CD8+cells expressing granz
Standard Deviation 0.49
|
|
Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood
Pre-treatment
|
34.7 percentage of CD8+cells expressing granz
Standard Deviation 0.48
|
Adverse Events
Nivolumab
Serious events: 1 serious events
Other events: 17 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Nivolumab
n=17 participants at risk
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Blood and lymphatic system disorders
Hypercalcemia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
Other adverse events
| Measure |
Nivolumab
n=17 participants at risk
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Nivolumab: 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.
|
|---|---|
|
Skin
Rash acneiform
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Skin
Pruritic Rash Shoulder
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Skin
Psoriasis
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Skin
Actinic Keratosis
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Vascular disorders
Hypertension
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
General disorders
Painful Swelling In R Submandibular Node
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papilloma
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Ear and labyrinth disorders
Ear Pain
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Ear and labyrinth disorders
Hearing Impaired
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Constipation
|
47.1%
8/17 • Number of events 8 • 12 months post surgery
|
|
Gastrointestinal disorders
Nausea
|
17.6%
3/17 • Number of events 3 • 12 months post surgery
|
|
General disorders
Oral Pain
|
17.6%
3/17 • Number of events 3 • 12 months post surgery
|
|
Gastrointestinal disorders
Diarrhea
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
Gastrointestinal disorders
Dysphagia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
muscositis oral
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Thrush
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Worsened Tongue Pain
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Xerostomia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Numbness Of Tongue
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Opiod Induced Constipation
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Gastrointestinal disorders
Tongue Pain
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
General disorders
Fatigue
|
23.5%
4/17 • Number of events 4 • 12 months post surgery
|
|
General disorders
Pain
|
23.5%
4/17 • Number of events 4 • 12 months post surgery
|
|
General disorders
Edema Face
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
General disorders
Worsened Appetite
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
Infections and infestations
Sinusitis
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Infections and infestations
Leg Wound Infection At Site Of Graft
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Investigations
Weight Loss
|
29.4%
5/17 • Number of events 5 • 12 months post surgery
|
|
Investigations
Alanine aminotransferase increased
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Investigations
Creatinine increased
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Metabolism and nutrition disorders
Hypokalemia
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Right Hand Swollen
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Stiffness in Arms/Legs
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
T8 Compression Deformity
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Back Spasms
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Arthritis Feeling In Thighs And Arms
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Musculoskeletal and connective tissue disorders
Stiff Neck
|
11.8%
2/17 • Number of events 2 • 12 months post surgery
|
|
Psychiatric disorders
Anxiety
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Psychiatric disorders
Insomnia
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.9%
1/17 • Number of events 1 • 12 months post surgery
|
Additional Information
Alan Brisendine, Sponsor-Investigator Support Unit Manager
Medical University of South Carolina
Phone: 843-792-9007
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place