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

Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03021993

Enrollment

Registered

2017-01-16

Start date

2017-05-30

Completion date

2021-11-15

Last updated

2025-11-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Oral Cavity SCC

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.

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.

Interventions

DRUGNivolumab

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 design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. 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 2. Greater than or equal to 18 years of age 3. ECOG performance status of 0 or 1 4. 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) 5. 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.

Exclusion criteria

1. Prior immunotherapy or treatment with another anti PD 1 agent 2. Prior chemotherapy including Cetuximab or radiation therapy 3. Previous severe hypersensitivity reaction to another monoclonal antibody 4. Women who are pregnant, lactating or expecting to conceive 5. Men who are expecting to father children within the research period 6. Known history of HIV or AIDS 7. Positive test for HBV sAg or HCV antibody indicating acute or chronic infection 8. Concomitant malignancies except cutaneous squamous cell carcinoma or basal cell carcinoma 9. Unresectable primary tumor or regional disease; presence of distant metastases. 10. History of pneumonitis or interstitial lung disease 11. 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 12. 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

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate Using Pathological Response	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.

Secondary

Measure	Time frame	Description
Level of Activated T-cells in Peripheral Blood	Day 1 and time of surgery (day 36 or day 50)	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.
Level of Immune Stimulatory Cytokines in Peripheral Blood	Day 1 and time of surgery (day 36 or day 50)	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.
Level of Treg Cells in Peripheral Blood Using Immunostaining	Day 1 and time of surgery (day 36 or day 50)	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.
Expression of Granzyme-B in CD8+ Cells From Peripheral Blood	Day 1 and time of surgery (day 36 or day 50)	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.
Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood	Day 1 and time of surgery (day 36 or day 50)	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.
Expression of IFN-gamma in CD4+ Cells	Day 1 and time of surgery (day 36 or day 50)	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	17
Total	17

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	3
Overall Study	enrolled but were not treated	1
Overall Study	Physician Decision	1
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Nivolumab
Age, Continuous	62.6 years
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	16 Participants
Region of Enrollment United States	17 participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	10 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	3 / 17
other Total, other adverse events	17 / 17
serious Total, serious adverse events	1 / 17

Outcome results

Primary

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 frame: Time of surgery (day 36 or day 50)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Nivolumab	Objective Response Rate Using Pathological Response	4 Participants

Secondary

Expression of CD8+ Cells Expressing Granzyme B (Cytolytic Response) From Peripheral Blood

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.

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