Safety and Tolerability of LDRT Plus Concurrent Partial SBRT and Tislelizumab in Patients With Bulky Tumors

Официальное название

Safety and Tolerability of Low Dose Radiotherapy Plus Concurrent Partial Stereotactic Ablative Radiotherapy (Eclipse-RT) and Tislelizumab in Patients With Bulky Tumors

Обзор

This is a 3+3 dose escalation phase I study which aims to evaluate the safety and tolerability of low dose radiotherapy (LDRT) plus concurrent partial Stereotactic Ablative Radiotherapy (SBRT) and Tislelizumab in Patients with bulky tumors who have failed standard therapy. At least 9 participants will be enrolled in this study.

Подробное описание

This is 3+3 escalation phase I study which will be conducted in West China Hospital.

Step A: A dose escalation of low dose radiotherapy (LDRT) and partial SBRT, at least 3 patients per cohort (a total of at least 9 patients) will be enrolled to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose for expansion (RDE) for lung LDRT and partial SBRT.

All eligible patients will receive LDRT + partial SBRT and Tislelizumab at different dose levels (described as below). Tislelizumab will be given at 200mg as recommended in the instruction manual every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or Tislelizumab reaches a maximum of up to 24 months.

Patients in the dose escalation will receive LDRT + partial SBRT at 3 cohorts with increasing dose levels: 6 Gy (2 Gy/f) + 24 Gy (8 Gy/f); 6 Gy (2 Gy/f) + 30 Gy (10 Gy/f); 6 Gy (2 Gy/f) + 45 Gy (15 Gy/f).

Step B: A dose expansion of LDRT + partial SBRT A cohort of 15 patients will receive lung LDRT and partial SBRT at the RDE determined during the dose-escalation phase in combination with PD-1 inhibitors to obtain additional safety and response data.

Вмешательства

• Препарат Tislelizumab
  Patients will receive treatment with Tislelizumab (200 mg, iv, d1), every 3 weeks for a maximum of 48 months.
• Лучевая терапия Low Dose Radiotherapy
  LDRT (d1-d3): 6Gy/3f with conventional external beam radiation.
• Лучевая терапия Stereotactic Ablative Radiotherapy
  Partial SBRT at dose escalation levels: 24Gy/3f, 30Gy/3f, 45Gy/3f.

Первичные конечные точки

• Dose Limiting Toxicities [Срок оценки: 24 months]

Вторичные конечные точки (3)

• Objective Response Rate (ORR) [Срок оценки: up to 24 months after the enrollment]
• Progression Free Survival (PFS) [Срок оценки: up to 24 months after the enrollment]
• Overall Survival (OS) [Срок оценки: up to 24 months after the enrollment]

Критерии участия

Критерии включения

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• Patients with histologically or cytologically confirmed stage IV solid tumours.
• Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.
• Patients who have failed the standard therapy, or who are unsuitable for standard treatment, or refuse chemotherapy.
• At least one measurable lesion according to RECIST 1.1. A lesion that has previously received radiotherapy can be considered a target lesion only if this lesion is clearly progressed after radiotherapy.
• The target lesions (irradiated lesions) are > 5cm in in diameter
• ECOG 0-2.
• Life expectancy of > 3 months.
• Subjects should agree to use an adequate method of contraception.

Критерии исключения

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or spinal cord compression, etc.
• With oncologic emergencies that require immediate treatment
• EGFR/ALK/ROS-1 mutation or mutation status unknown.
• Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis (drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.
• History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway obstruction disease
• Patients with peripheral neuropathy.
• Significant heart disease or impairment of cardiac function
• Fluid accumulating in the third space, such as pericardial effusion, pleural effusion and peritoneal effusion that remains uncontrolled by aspiration or other treatment
• Known allergy to drugs or excipients, known severe allergic reaction to any of the PD-1 monoclonal antibodies
• Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital, Sichuan University — Чэнду

Публикации

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Идентификаторы

NCT: NCT06349837 · ECLIPSE-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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