Anticancer Therapeutic Vaccination Using Telomerase-derived Universal Cancer Peptides in Glioblastoma (UCPVax-Glio)

• ClinicalTrials.gov Identifier: NCT04280848
• Recruitment Status: Recruiting
• First Posted: February 21, 2020
• Last Update Posted: July 31, 2020
• Sponsor: Centre Hospitalier Universitaire de Besancon
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Besancon

Tracking Information

• First Submitted Date: February 17, 2020
• First Posted Date: February 21, 2020
• Last Update Posted Date: July 31, 2020
• Actual Study Start Date: May 26, 2020
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2020)

Immunogenicity [ Time Frame: at day 60 ]

Anti-TERT specific T cell responses measured in peripheral blood using IFN-gamma ELISPOT

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Anticancer Therapeutic Vaccination Using Telomerase-derived Universal Cancer Peptides in Glioblastoma
• Official Title: Anticancer Therapeutic Vaccination Using Telomerase-derived Universal Cancer Peptides in Glioblastoma

Brief Summary

Glioblastoma (GBM) is the most frequent primary brain tumor and the brain tumor with the poorest prognosis. The current treatment relies on surgical resection of gross tumor followed by radiochemotherapy and adjuvant therapy with temozolomide.

After such therapy, most patients experiment recurrence and few therapeutic option are available. Despite such therapies, median survival only reaches around fifteen months.

There is a strong rational to develop telomerase vaccine in GBM. Telomerase (TERT) is a major oncogene, particularly in primary brain tumors 24. Alterations in TERT are very frequent in central nervous system tumors, seen most commonly in gliomas25. Mutations in the TERT promoter are found in approximately 80% of primary glioblastoma (GBM). These findings strongly support the rational to develop vaccine targeting telomerase in GBM.

The aim of this project is to evaluate UCPVax treatment in glioblastoma. UCPVax is a therapeutic anti-cancer vaccine based on the telomerase-derived helper peptides designed to induce strong TH1 CD4 T cell responses in cancer patients (NCT02818426).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glioblastoma

Intervention

Drug: UCPVax

The UCPVax vaccination protocol will start at least one month after glioblastoma patients have completed the concomitant radiochemotherapy (Radiotherapy + Temozolomide RT/TMZ), without the 6 additional monthly cures of temozolomide, with a maximum of 45 days.

UCPVax vaccine will be emulsified in Montanide ISA 51 and injected subcutaneously at days 1, 8, 15, 29, 36 and 43 (priming phase) following by boost vaccination one month after the last injection and then every 8 weeks for 12 months maximum.

Study Arms

Experimental: UCPVax vaccine

UCPVax is a therapeutic vaccine derived from telomerase combined with Montanide ISA51 VG as adjuvant.

Intervention: Drug: UCPVax

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 20, 2020): 28
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female patients, age ≥ 18 and ≤ 75 years old
• Written informed consent
• Histologically confirmed glioblastoma
• Patient with unmethylated MGMT (Methyl guanine methyl transferase) status
• Patients previously pre-treated with standard radiochemotherapy (without the additional cures of temozolomide.)
• Karnofsky Performance status ≥ 70%
• Life-expectancy > 3 months
• Adequate hematological, hepatic, and renal function.
• Females must be using highly effective contraceptive measures , and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential.

Females of childbearing potential should use reliable methods of contraception from the time of the screening until 5 weeks after discontinuing study treatment.

Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 5 months following discontinuation of study drug. Patients should refrain from donating sperm from the start of dosing until 5 months after discontinuing study treatment.

- Affiliation to French social security or receiving such a regime.

Exclusion Criteria:

• Presence of known extracranial metastatic or leptomeningeal disease Glioblastoma with mutated IDH1 (assessed by Immunohistochemistry)
• Current or recent treatment with another investigational drug
• Carmustine implant during surgery
• History of autoimmune diseases (lupus, rheumatoid arthritis, inflammatory bowel disease…)

• Prohibited medications:

  1. Chronic treatment with immunosuppressive drugs
  2. Ongoing requirement for supraphysiologic steroid defined as >10 mg prednisone daily (or equivalent)
  3. Treatment with therapeutic oral or IV antibiotics within 4 weeks prior to enrollment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or pulmonary disease) are eligible for the study
• Known positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C virus (HCV); presence in the serum of the antigens HBs
• Non-hematologic toxicities Grade >1 severity (or, at the investigator's discretion, Grade >2 if not considered a safety risk for the patient).
• Patient with intra-alveolar hemorrhage, pulmonary fibrosis, or uncontrolled asthma, or chronic obstructive disease (COPD), defined as at least 1 hospitalization within 4 months prior to enrollment or as at least 3 exacerbations during the last year prior to enrollment Hospitalization for cardiovascular or pulmonary disease within 4 weeks prior to enrollment.
• Patients with LEVF<40%
• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment or patient in the exclusion period of a previous clinical trial.
• Pregnancy or lactating patients.
• Patients with any severe/uncontrolled inter current illness, significant co morbid or psychiatric conditions that in the opinion of the investigator would impair study participation or cooperation.
• Patients under guardianship, curatorship or under the protection of justice.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Olivier ADOTEVI, Pr; +33381668166; olivier.adotevi@univ-fcomte.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04280848
• Other Study ID Numbers: N/2013/67
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Centre Hospitalier Universitaire de Besancon
• Study Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: Not Provided

Investigators

• Principal Investigator: Clotilde VERLUT, Dr; CHU Besançon

• PRS Account: Centre Hospitalier Universitaire de Besancon
• Verification Date: July 2020