Clinical Trials /

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

NCT03021993

Description:

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.

Related Conditions:
  • Oral Cavity Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 102510
  • NCT ID: NCT03021993

Conditions

  • Oral Cavity SCC

Interventions

DrugSynonymsArms
NivolumabOPDIVONivolumab

Purpose

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.
    

Trial Arms

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

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate using pathological response
Time Frame:Time of surgery (day 36 or day 50)
Safety Issue:
Description: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 Outcome Measures

Measure:Level of Treg cells in peripheral blood using immunostaining
Time Frame:Day 1 and time of surgery (day 36 or day 50)
Safety Issue:
Description: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.
Measure:Level of activated T-cells in peripheral blood
Time Frame:Day 1 and time of surgery (day 36 or day 50)
Safety Issue:
Description: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.
Measure:Level of immune stimulatory cytokines in peripheral blood
Time Frame:Day 1 and time of surgery (day 36 or day 50)
Safety Issue:
Description: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.
Measure:Expression of Th1 responses in CD4+ cells from peripheral blood
Time Frame:Day 1 and time of surgery (day 36 or day 50)
Safety Issue:
Description: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.
Measure:Expression of Th2 responses in CD4+ cells from peripheral blood
Time Frame:Day 1 and time of surgery (day 36 or day 50)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Medical University of South Carolina

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