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

Gliknik Inc.33 sites in 7 countries80 target enrollmentMarch 30, 2017

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 30, 2017

End Date

May 25, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Gliknik Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age \> 18 years
•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
•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
•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.
•No history of distant metastases.
•Tumor tissue from surgery or biopsy must be available to determine MAGE-A3 expression for correlative studies.
•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/m

Exclusion Criteria

•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.
•Subjects with active autoimmune disease or a history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment.
•Subjects who have used systemic corticosteroids or other immunosuppressants for any condition within 14 days of randomization. Inhaled or topical steroids are permitted.
•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
•Major surgery or traumatic injury within 28 days of randomization
•Prior splenectomy or organ allograft
•Any other prior, concurrent or planned chemotherapy, immunotherapy, radiotherapy, device, or investigational therapy for this cancer other than those specified in this study.
•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.
•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).
•Known hypersensitivity to cyclophosphamide, its metabolites or any other components, or known urinary outflow obstruction.

Arms & Interventions

GL-0817

Subjects 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.

Intervention: GL-0817

GL-0817

Subjects 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.

Intervention: Hiltonol

GL-0817

Subjects 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.

Intervention: Sargramostim

GL-0817

Subjects 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.

Intervention: cyclophosphamide

Placebo

Subjects 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.

Intervention: Placebo