Oncolytic Virus H101 Combined With Lenvatinib Plus Toripalimab Compared With FOLFOX in Patients With Advanced Biliary Tract Cancer (OPTIONS-06)

Официальное название

Oncolytic Virus H101 Combined With Lenvatinib Plus Toripalimab Compared With FOLFOX in Patients With Advanced Biliary Tract Cancer (OPTIONS-06): a Multicenter, Randomized, Phase 2 Study

Обзор

This study will evaluate the efficacy and safety of Oncolytic virus H101 combined with lenvatinib plus Toripalimab compared with FOLFOX in patients with advanced biliary tract cancer (BTC) who have progressed after first-line treatment.

Подробное описание

The participants will be randomized in a 1:1 ratio to one of the two treatment arms: Arm A (experimental arm): H101 + lenvatinib + Toripalimab; Arm B (control arm): FOLFOX

Вмешательства

• Препарат TORIPALIMAB INJECTION(JS001 )
  Toripalimab will be administered by IV, 240 mg on day 1 of each 21 day cycle until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
• Препарат Lenvatinib
  Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
• Препарат H101
  H101 will be percutaneously injected into tumor on day 1 of every 21-day cycle. Lenvatinib plus Toripalizumab will be administered 1-3 days after H101 injection.
• Препарат FOLFOX
  FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m², leucovorin, 400 mg/m2, fluorouracil 400 mg/m² \[bolus\], and fluorouracil 2400 mg/m² as a 46-h continuous intravenous infusion

Первичные конечные точки

• Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 42 months]

Вторичные конечные точки (7)

• Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 24 months]
• Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 24 months]
• Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 24 months]
• Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 24 months]
• Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 [Срок оценки: max 24 months]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Срок оценки: max 42 months]
• Translational study [Срок оценки: max 42 months]

Критерии участия

Критерии включения

• Written informed consent obtained.
• Age ≥ 18 years at time of study entry.
• Participants must have unresectable or metastatic histologically or cytologically confirmed biliary tract cancer.
• Participants must have failed 1 line of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
• At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
• Performance status (PS) ≤ 2 (ECOG scale).
• Life expectancy of at least 12 weeks.
• Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

Критерии исключения

• History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
• Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
• Prior treatment with oncolytic virus.
• Prior treatment with Lenvatinib or other targeted therapy.
• RFA and resection administered less than 4 weeks prior to study treatment start.
• Radiotherapy administered less than 4 weeks prior to study treatment start.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
• Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
• Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to: a) history of interstitial lung disease b) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) c) known acute or chronic pancreatitis d) active tuberculosis e) any other active infection (viral, fungal or bacterial) requiring systemic therapy f) history of allogeneic tissue/solid organ transplant g) diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. i) Live vaccine within 30 days prior to the first dose of treatment or during study treatment. j) History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
• Medication that is known to interfere with any of the agents applied in the trial.
• Any other efficacious cancer treatment except protocol specified treatment at study start.
• Patient has received any other investigational product within 28 days of study entry.
• Prior therapy with an anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). \[Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner\]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

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

Китай · 1 центр

• Zhongshan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT06919848 · OPTIONS-06

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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