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

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ClinicalTrials.gov Identifier: NCT03021993
Recruitment Status : Recruiting
First Posted : January 16, 2017
Last Update Posted : May 2, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Medical University of South Carolina

Tracking Information
First Submitted Date  ICMJE December 20, 2016
First Posted Date  ICMJE January 16, 2017
Last Update Posted Date May 2, 2019
Actual Study Start Date  ICMJE May 30, 2017
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2017)
Objective response rate using pathological response [ Time Frame: Time of surgery (day 36 or day 50) ]
Change History Complete list of historical versions of study NCT03021993 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2017)
  • Level of Treg cells in peripheral blood using immunostaining [ Time Frame: 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.
  • Level of activated T-cells in peripheral blood [ Time Frame: 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 [ Time Frame: 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.
  • Expression of Th1 responses in CD4+ cells from peripheral blood [ Time Frame: Day 1 and time of surgery (day 36 or day 50) ]
    Expression of IL-2 (Th1 responses) 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.
  • Expression of Th2 responses in CD4+ cells from peripheral blood [ Time Frame: Day 1 and time of surgery (day 36 or day 50) ]
    Expression of IIL 10 (Th2 responses) 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.
  • Expression of CD8+ cells expressing granzyme B (ctolytic response) from peripheral blood [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2017)
  • 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 Th1 responses in CD4+ cells from peripheral blood [ Time Frame: Day 1 and time of surgery (day 36 or day 50) ]
  • Expression of Th2 responses in CD4+ cells from peripheral blood [ Time Frame: Day 1 and time of surgery (day 36 or day 50) ]
  • Expression of CD8+ cells expressing granzyme B (ctolytic response) from peripheral blood [ Time Frame: Day 1 and time of surgery (day 36 or day 50) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Official Title  ICMJE Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Oral Cavity SCC
Intervention  ICMJE Drug: 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.
Other Name: OPDIVO
Study Arms  ICMJE Experimental: Nivolumab
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 13, 2017)
19
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Newly diagnosed histologically proven locoregional OCSCC (T stage 2-4) without evidence of distant metastases. OCSCC includes the subsites of oral tongue, floor of mouth, gingiva, retromolar trigone, and buccal mucosa OR

Recurrent or persistent histologically proven locoregional OCSCC (recurrent T-stage 2-4) that was initially treated with surgery alone. To allow sufficient tumor tissue for the immunological analyses, patients with T1 OCSCC will be excluded. Eligibility criteria will also include the following:

  • Greater than or equal to 18 years of age
  • ECOG performance status of 0 or 1
  • Must meet screening lab criteria outlined in the protocol
  • 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 (ie, who are postmenopausal or surgically sterile and azoospermic men are not required to use contraception.

Exclusion Criteria:

  • 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 or 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.
  • 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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vistea Crawford 843-792-9321 hcc-clinical-trials@musc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03021993
Other Study ID Numbers  ICMJE 102510
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Medical University of South Carolina
Study Sponsor  ICMJE Medical University of South Carolina
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: David Neskey, MD Medical University of South Carolina
PRS Account Medical University of South Carolina
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP