Clinical Trials /

Safety and Efficacy Study of GL-0817 (With Cyclophosphamide) for the Prevention of Recurrence of Squamous Cell Carcinoma of the Oral Cavity

NCT02873819

Description:

This is a multi-center, randomized, double-blind clinical trial to assess the safety and efficacy of GL-0817 as a means to prevent disease recurrence in patients considered at high-risk following surgery and adjuvant chemoradiotherapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of GL-0817 (With Cyclophosphamide) for the Prevention of Recurrence of Squamous Cell Carcinoma of the Oral Cavity
  • Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Determine the Safety and Efficacy of GL-0817 (With Cyclophosphamide) for the Prevention of Recurrence in HLA-A2+ Patients With High-Risk Squamous Cell Carcinoma of the Oral Cavity

Clinical Trial IDs

  • ORG STUDY ID: GL0817-01
  • SECONDARY ID: 2016-001256-22
  • NCT ID: NCT02873819

Conditions

  • Squamous Cell Carcinoma of the Oral Cavity

Interventions

DrugSynonymsArms
GL-0817Biropepimut-SGL-0817
HiltonolPoly-ICLCGL-0817
SargramostimGM-CSF, LeukineGL-0817
cyclophosphamideGL-0817
PlaceboPlacebo

Purpose

This is a multi-center, randomized, double-blind clinical trial to assess the safety and efficacy of GL-0817 as a means to prevent disease recurrence in patients considered at high-risk following surgery and adjuvant chemoradiotherapy.

Trial Arms

NameTypeDescriptionInterventions
GL-0817ExperimentalSubjects in active treatment will be vaccinated with GL-0817 with the adjuvants Poly-ICLC (Hiltonol®) and GM-CSF (Sargramostim, Leukine®) 3 times at 3-week intervals followed by 7 doses at 3-month intervals beginning at Week 18. Patients will receive IV Cyclophosphamide 1 day prior to the first 3 vaccinations.
  • GL-0817
  • Hiltonol
  • Sargramostim
  • cyclophosphamide
PlaceboPlacebo ComparatorSubjects in placebo arm will receive placebo to cyclophosphamide (normal saline solution) followed by Poly-ICLC/GM-CSF/placebo vaccine injections on the same schedule as the GL-0817 cohort.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Age > 18 years

          2. Histologic diagnosis of squamous cell carcinoma of the oral cavity including the lip,
             floor of mouth, anterior 2/3 of tongue, alveolus and gingiva, buccal mucosa, hard
             palate and retromolar trigone

          3. Subjects must have undergone primary gross total resection (no re-resected patients
             are allowed) with fulfillment of at least 1 of the following histologic criteria for
             high-risk disease:

               -  Histologic involvement of 2 or more regional lymph nodes

               -  Any lymph node with histologic extracapsular extension (ECS)

               -  Close (<3mm) or positive surgical margins on microscopic evaluation with no gross
                  residual tumor

          4. No evidence of locoregional disease or distant metastases at screening. Subjects must
             have negative scans (CT, CT-PET or MRI) for locoregional recurrence, brain or lung
             metastases. A negative biopsy will be mandated in patients with a positive scan. Other
             evaluations should be performed as clinically indicated.

          5. No history of distant metastases.

          6. Tumor tissue from surgery or biopsy must be available to determine MAGE-A3 expression
             for correlative studies.

          7. Following surgery, the patient must have received external beam radiotherapy (58-66 Gy
             in 2 Gy fractions, 5 days per week) with concomitant cisplatin starting within 8 weeks
             of surgery. A brief delay in the initiation of radiotherapy following 8 weeks
             post-surgery due to administrative reasons (e.g., start of RT on Mondays) may be
             permitted by the Medical Monitor. The cumulative dose of cisplatin the subject
             received must be > 150 mg/m2. Protocol therapy must be initiated within a period of
             4-8 weeks (28-56 days) following the end of RT.

          8. The patient is, in the investigator's opinion, adequately recovered from the effects
             of surgery and chemoradiotherapy to participate in this study.

          9. Blood HLA-A2 phenotype

         10. ECOG Performance Status < 1

         11. Laboratory values obtained ≤ 14 days prior to randomization:

               -  Absolute neutrophil count (ANC) ≥ 1500/μL (without intervention, e.g., G-CSF)

               -  Platelets ≥ 75,000/μL (without intervention, e.g., transfusion)

               -  Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥8.0 g/dl is acceptable).

               -  Alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN)

               -  AST and ALT ≤ 2 x ULN

               -  Creatinine < 2 x ULN

               -  Bilirubin < 1.5x ULN (except for patients with Gilbert's disease, for whom the
                  upper acceptable limit of serum bilirubin is 3mg/dL)

         12. A female subject is eligible to enter the study if she is:

               -  not pregnant or nursing; Female participants must not breastfeed during the study
                  and for a period of 30 days following the last dose.

               -  of non-childbearing potential (i.e., women who had a hysterectomy, are
                  postmenopausal which is defined as 1 year without menses, have both ovaries
                  surgically removed or have current documented tubal ligation); or

               -  of childbearing potential (i.e., women with functional ovaries and no documented
                  impairment of oviductal or uterine function that would cause sterility). This
                  category includes women with oligomenorrhea [even severe], women who are
                  perimenopausal or have just begun to menstruate. These women must have a negative
                  serum pregnancy test at screening, and agree to one of the following:

                    -  complete abstinence from intercourse from 2 weeks prior to administration of
                       the 1st dose of study agent and 6 months after the last dose of study agent;
                       or

                    -  consistent and correct use of 1 of the following highly effective methods of
                       birth control for one month prior to the start of the study agent and 6
                       months after the last dose:

               -  combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation (oral, intravaginal, transdermal)

               -  progestogen-only hormonal contraception associated with inhibition of ovulation
                  (oral, injectable, implantable)

               -  intrauterine device (IUD)

               -  intrauterine hormone-releasing system ( IUS)

               -  bilateral tubal occlusion

               -  vasectomized partner (if vasectomized is the sole sexual partner and has received
                  medical confirmation of surgical success)

         13. A male subject who is sexually active with a woman of childbearing potential is
             eligible to enter the study if he agrees to use effective contraception throughout the
             study and for 6 months after the last dose of study agent.

         14. The subject must be capable of understanding the investigational nature, potential
             risks and benefits of the study and capable of providing valid informed consent. The
             subject must provide study specific informed consent prior to any protocol procedures
             that are not a part of standard care, including consent for assessment of HLA-A2
             status, mandatory tissue submission for MAGE-A3 analysis and correlative studies.

         15. The subject must be willing to return to the study center for vaccinations and
             study-related follow up procedures including blood and tumor collections and
             completion of imaging studies as required by the protocol.

        Exclusion Criteria:

          1. Known HIV or hepatitis B/C infection (testing not required). Subjects who are
             hepatitis C antibody positive may be enrolled if they are confirmed to have a negative
             viral load at screening.

          2. Subjects with active autoimmune disease or a history of autoimmune disease requiring
             systemic steroids or other immunosuppressive treatment.

          3. Subjects who have used systemic corticosteroids or other immunosuppressants for any
             condition within 14 days of randomization. Inhaled or topical steroids are permitted.

          4. Any medical condition which would, in the investigator's opinion, compromise the
             patient's ability to mount an immune response, renders the patient a poor candidate
             for this trial or could confound the results of the study

          5. Major surgery or traumatic injury within 28 days of randomization

          6. Prior splenectomy or organ allograft

          7. Any other prior, concurrent or planned chemotherapy, immunotherapy, radiotherapy,
             device, or investigational therapy for this cancer other than those specified in this
             study.

          8. History of other malignancy (i.e., excluding disease under study) within 3 years of
             randomization. Exceptions include: adequately-treated basal cell or squamous cell skin
             cancer, carcinoma in situ of the cervix or breast, or adequately treated
             non-metastatic prostate cancer.

          9. Known hypersensitivity to GM-CSF, yeast-derived products or any component of the
             GM-CSF drug product (e.g., mannitol) or poly-ICLC (e.g., carboxymethylcellulose).

         10. Known hypersensitivity to cyclophosphamide, its metabolites or any other components,
             or known urinary outflow obstruction.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free interval
Time Frame:Up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease-free survival (DFS)
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:up to 5 years
Safety Issue:
Description:
Measure:Disease-free interval in a per protocol analysis
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Adverse event profile
Time Frame:up to week 94
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gliknik Inc.

Last Updated