Evaluation of the Interest to Combine a CD4 Th1-inducer Cancer Vaccine Derived From Telomerase and Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Официальное название

Evaluation of the Interest to Combine a CD4 Th1-inducer Cancer Vaccine Derived From Telomerase and Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: a Proof of Concept Randomized Phase II Study (TERTIO - Prodige 82)

Обзор

The TERTIO trial will propose to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with anti-PD-L1 therapy (atezolizumab) and bevacizumab in unresectable HCC by evaluation of the objective response rate at 6 months (randomized phase II, 10 centers, 105 patients)

Вмешательства

• Препарат Atezolizumab
  1200 mg IV every 3 weeks until disease progression or unacceptable toxicity
• Препарат Bevacizumab
  15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity
• Препарат UCPVax
  UCPVax vaccine (combined with Montanide ISA51 as adjuvant) at 0.5 mg subcutaneously

Первичные конечные точки

• objective response rate (ORR) [Срок оценки: at 6 months]

Вторичные конечные точки (3)

• overall survival (OS) [Срок оценки: through study completion, an average of 2 years]
• progression-free-survival (PFS) [Срок оценки: through study completion, an average of 2 years]
• disease control rate (DCR) [Срок оценки: at 6 months]

Критерии участия

Main inclusion Criteria:

• Signed informed consent
• Histologically confirmed hepatocellular carcinoma
• Locally advanced, metastatic, or unresectable disease
• Patient who had not previously received systemic anti-cancer treatment
• Age ≥ 18 years
• Measurable disease defined according to mRECIST guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
• Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to National Cancer Institute \[NCI\] common terminology criteria for adverse events, version 5 (CTCAE v5) with the exception of Grade 2 alopecia
• Performance status < 2
• Child-Pugh Class A status
• BCLC C stage or BCLC B stage not eligible to loco-regional therapy according to the Barcelona Clinic Liver Cancer (BCLC) staging system

Main exclusion Criteria:

Non-eligible to a clinical trial:

• Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy.
• Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer
• Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
• Current participation in a study of an investigational agent or in the period of exclusion
• Patient under guardianship, curatorship or under the protection of justice

Cancer-specific exclusion criteria:

• Know fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula
• Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to inclusion. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
• Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed

Non-eligible to treatment:

• History of encephalopathy
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 14 центров

• CHU de Besançon — Besançon
• CH William Morey — Chalon-sur-Saône
• Hôpital Henri Mondor — Créteil
• Centre Georges François Leclerc — Dijon
• Hôpital Nord Franche-Comté — Montbéliard
• CHU de Montpellier — Montpellier
• CH de Mulhouse — Mulhouse
• Institut de Cancérologie de l'Ouest — Nantes
• … и ещё 6 центров

Публикации

• Vienot A, Jacquin M, Rebucci-Peixoto M, Pureur D, Ghiringhelli F, Assenat E, Hammel P, Rosmorduc O, Stouvenot M, Allaire M, Bouattour M, Regnault H, Fratte S, Raymond E, Soularue E, Husson-Wetzel S, Di Martino V, Muller A, Clairet AL, Fagnoni-Legat C, Adotevi O, Meurisse A, Vernerey D, Borg C. Evaluation of the interest to combine a CD4 Th1-inducer cancer vaccine derived from telomerase and atezol PMID 37516867

Идентификаторы

NCT: NCT05528952 · 2022/680

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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