This study (phase I clinical trial and expansion cohorts) will evaluate safety and efficacy of combination of atezolizumab and tiragolumab, with concomitant or sequential SBRT for four oligometastatic cancer cohorts. This study will allow to developpe one or several randomized Phase II clinical trials for the more promising indications
This study will be composed of 2 stepms. First step will be a phase I with the aim to establish the recommended safety scheme of administration (concomitant or sequential) of tiragolumab + atezolizumab + SBRT. The phase I will enrolled only patients from the cohort 1 (metastatic non-small cell lung cancer). The second step will be an expansion cohorts phase at the recommended scheme of administration. The second step will enrolled patients from 4 different cohorts (metastatic non-small cell lung cancer, metastatic bladder cancer, metastatic renal cell carcinoma, metastatic head and neck carcinoma).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Treatment given every 21 days during 24 months or until progression
Treatment given every 21 days during 24 months or until progression
Radiothérapy is delivered as a hypofractionated schedule of 3 doses of 8Gy (idealy on Monday, Wednesday and Friday, or 3 sessions over a week, respecting at least 24 hours between each fraction)
Centre Georges François Leclerc (CGFL)
Dijon, Bourgogne-Franche-Comté, France
RECRUITINGPhase I : to evaluate safety of SBRT
Using the following DLTs (DLT are defined by the following events related to study treatments (SBRT and/or tiragolumab, atezolizumab) : * grade 3 pneumopathy (except if return to grade ≤2 within 7 days) * grade 3 radiation dermatitis (except if return to grade ≤2 within 2 weeks). * grade 4 of any other toxicity (except if return to ≤ G3 within 2 weeks) * for all any grade 4 adverse event which lead to treatment discontinuation of more than 7 days
Time frame: The first 5 weeks (35 days) after the first dose of study treatment for sequential administration (3X8 Gy of radiotherapy and 3 dosing of immunotherapy)
Phase I : to evaluate safety of SBRT
Using the following DLTs (DLT are defined by the following events related to study treatments (SBRT and/or tiragolumab, atezolizumab) : * grade 3 pneumopathy (except if return to grade ≤2 within 7 days) * grade 3 radiation dermatitis (except if return to grade ≤2 within 2 weeks). * grade 4 of any other toxicity (except if return to ≤ G3 within 2 weeks) * for all any grade 4 adverse event which lead to treatment discontinuation of more than 7 days
Time frame: the first 4 weeks (28 days) after the first dose of study treatement for concomitant administration (3X8 Gy of radiotherapy and 3 dosing of immunotherapies)
Expansion phase : The 6-month progression free survival (PFS) rate after SBRT, atezolizumab and tiragolumab combination.
Evaluation by analysis of PFS. PFS is defined as the time from inclusion to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1 and iRECIST, or death from any cause, whichever occurs first.It will be evaluated at 6 months.
Time frame: During 6 months after inclusion
Expansion cohort : The long term safety of SBRT, atezolizumab and tiragolumab antibodies combination
Evaluation by analysis of AAE. Will be evaluated with acute and late adverse events (AAEs) according to CTCAE 5.0 Treatment safety evaluation will be based on adverse event (AE) occurrence, the use of concomitant treatments, changes occuring in the course of treatment, observed during physical examination, in the vital signs (arterial pressure, pulse and body temperature), in electrocardiogram (ECG) and biological and clinical examinations (biochemistry, haematology).
Time frame: Throughout the treatment period (24 months)
Expansion cohort : overall survival (OS) following SBRT, atezolizumab and tiragolumab combination
Evaluation by analysis of Overall survival. Overall survival is defined as the time from inclusion to death to any cause
Time frame: Until the patient dies
Expansion cohort : Overall Response rate (ORR) and Non progression rate (NPR) following SBRT, atezolizumab and tiragolumab combination
Evaluation by analysis of ORR. ORR is evaluated from the first two evaluation scanner images carried out at 8-9 and 16-18 weeks after time from inclusion (CT-scan forecast after the 3rd and the 6th cure) as determined by the investigator according to RECIST v1.1 and iRECIST.
Time frame: 18 weeks after inclusion
Expansion cohort : The Duration of Response (DOR) and non progression duration (NPD) following SBRT, atezolizumab and tiragolumab combination
Evaluation by analysis of duration of Response (DOR). DOR is defined as time from documentation of disease complete or partial response to disease progression, defined according to RECISTv1.1 and iRECIST. Non Progression duration (NPD) is defined as time from documentation of disease complete response, partial response or stable disease to disease progression, defined according to RECISTv1.1 and iRECIST.
Time frame: Throughout the treatment period (24 months)
Expansion cohort : To evaluate abscopal effect
Un-irradiated metastasis volume(s) is evaluated from scanner images
Time frame: Throughout the treatment period (24 months)
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