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

NCT02873819 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: GL0817-012016-001256-22
• Study Type: interventional
• Target: 80
• Locations: 7 countries
• Sites: 33

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.

Conditions

Squamous Cell Carcinoma of the Oral Cavity

Outcome Measures

Primary Outcomes (1)

• Disease-free interval

  Up to 2 years

Secondary Outcomes (4)

• Disease-free survival (DFS)

  up to 2 years

• Overall survival (OS)

  up to 5 years

• Disease-free interval in a per protocol analysis

  up to 2 years

• Adverse event profile

  up to week 94

Study Arms (2)

GL-0817

EXPERIMENTAL

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.

Drug: GL-0817; Drug: Hiltonol; Drug: Sargramostim; Drug: cyclophosphamide

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

GL-0817 DRUG

GL-0817, IV at the dose 1.5 mg will be administered 3 times at 3-week intervals followed by 7 doses at 3-month intervals beginning at the Week 18 visit

Also known as: Biropepimut-S

GL-0817

Hiltonol DRUG

Hiltonol will be administered intramuscularly at the dose of 1.4 mg as adjuvant to GL0817, 3 times at 3-week intervals followed by 7 doses at 3-month intervals beginning at the Week 18 visit

Also known as: Poly-ICLC

GL-0817

Sargramostim DRUG

Sargramostim will be administered intramuscularly at the dose of 100 μg/m2, as adjuvant to GL0817, 3 times at 3-week intervals followed by 7 doses at 3-month intervals beginning at the Week 18 visit

Also known as: GM-CSF, Leukine

GL-0817

cyclophosphamide DRUG

cyclophosphamide will be administered IV at a dose of 200 mg/m2 (maximum dose 400 mg) one day prior to first three vaccinations of GL0817 with adjuvants

GL-0817

Placebo DRUG

Placebo (normal saline) will be administered as per the schedule of cyclophosphamide and GL0817/adjuvants administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/m2. Protocol therapy must be initiated within a period of 4-8 weeks (28-56 days) following the end of RT.
• The patient is, in the investigator's opinion, adequately recovered from the effects of surgery and chemoradiotherapy to participate in this study.
• Blood HLA-A2 phenotype
• ECOG Performance Status \< 1
• Laboratory values obtained ≤ 14 days prior to randomization:
• Absolute neutrophil count (ANC) ≥ 1500/μL (without intervention, e.g., G-CSF)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gliknik Inc.: lead

Study Sites (33)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

National Institute of Oncology

Budapest, Hungary

Location

Semmelweis University

Budapest, Hungary

Location

University of Debrecen Clinical Center

Debrecen, Hungary

Location

Bacs-Kiskun County Teaching Hospital

Kecskemét, Hungary

Location

Medical Center of the University of Pecs

Pécs, Hungary

Location

Oncology Center of Prof. Franciszek Lukaszczyk in Bydgoszcz

Bydgoszcz, Poland

Location

Swietokrzyskie Oncology Center in Kielce

Kielce, Poland

Location

Clinical Oncology Center

Omsk, Russia

Location

Rostov Oncology Research Institute

Rostov-on-Don, Russia

Location

Leningrad Regional Oncology Center

Saint Petersburg, Russia

Location

Oncology Center of Moskovskiy District

Saint Petersburg, Russia

Location

Ogarev Mordovia State University

Saransk, Russia

Location

Clinical Hospital #1

Sterlitamak, Russia

Location

Republican Clinical Oncology Center

Ufa, Russia

Location

Regional Clinical Oncology Hospital

Yaroslavl, Russia

Location

Institute of Oncology and Radiology of Serbia

Belgrade, Serbia

Location

Military Medical Academy, Clinic of Maxillofacial Surgery

Belgrade, Serbia

Location

Oncology Institute of Vojvodina (IOV), Clinic of Medical Oncology

Kamenitz, Serbia

Location

University Hospital Vall d'Hebron (HUVH)

Barcelona, Spain

Location

University Hospital La Paz

Madrid, Spain

Location

Parc Tauli Health Corporation

Sabadell, Spain

Location

Cherkasy Regional Oncology Center

Cherkasy, Ukraine

Location

Chernihiv Regional Oncology Center

Chernihiv, Ukraine

Location

Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital

Dnipro, Ukraine

Location

Ivano-Frankivsk Regional Oncology Center

Ivano-Frankivsk, Ukraine

Location

Communal Non-profit enterprise "Regional Center of Oncology"

Kharkiv, Ukraine

Location

Kyiv Regional Oncology Center

Kyiv, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, Ukraine

Location

Odesa Regional Oncology Center

Odesa, Ukraine

Location

Poltava Regional Clinical Oncology Center

Poltava, Ukraine

Location

Sumy Regional Clinical Oncology Center

Sumy, Ukraine

Location

Podillia Regional Oncology Center

Vinnytsia, Ukraine

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

poly ICLC; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Cyclophosphamide

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 22, 2016
• Study Start: March 30, 2017
• Primary Completion: May 17, 2021
• Study Completion: May 25, 2021
• Last Updated: March 8, 2022

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (8); HU (5); SE (3); ES (3); US (1); UA (11); PL (2)