Study Evaluating the Safety and the Efficacy of Combination of Atezolizumab, Tiragolumab and and Stereotactic Body Radiation Therapy in Patients With Oligometastatic Multiorgan (IMMUNOs-SBRT)

NCT05259319 | Unknown Phase 1

• 1 other identifier: 2021-003848-25
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Non Small Cell Lung Cancer; Metastatic Bladder Cancer; Metastatic Renal Cell Carcinoma; Metastatic Head and Neck Cancer

Keywords

Atezolizumab; Tiragolumab; Cancer; Stereotactic body radiation therapy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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)

Secondary Outcomes (6)

• Expansion phase : The 6-month progression free survival (PFS) rate after SBRT, atezolizumab and tiragolumab combination.

  During 6 months after inclusion

• Expansion cohort : The long term safety of SBRT, atezolizumab and tiragolumab antibodies combination

  Throughout the treatment period (24 months)

• Expansion cohort : overall survival (OS) following SBRT, atezolizumab and tiragolumab combination

  Until the patient dies

• Expansion cohort : Overall Response rate (ORR) and Non progression rate (NPR) following SBRT, atezolizumab and tiragolumab combination

  18 weeks after inclusion

• Expansion cohort : The Duration of Response (DOR) and non progression duration (NPD) following SBRT, atezolizumab and tiragolumab combination

  Throughout the treatment period (24 months)

Study Arms (1)

Atezolizumab + Tiragolumab + SBRT

EXPERIMENTAL

Atezolizumab + Tiragolumab (every 21 days during 24 months or until progression) + SBRT (treatment will be delivered on 5 days). The combination of SBRT and Immunotherapies will be performed using to different schemes. For the 6 first inclusions the combination will use a sequential scheme. If the safety criteria are respected the following patients will be able to be treated by concomitant scheme.

Drug: Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ]; Drug: Tiragolumab; Radiation: Stereotactic body radiation therapy (SBRT)

Interventions

Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ] DRUG

Treatment given every 21 days during 24 months or until progression

Atezolizumab + Tiragolumab + SBRT

Tiragolumab DRUG

Treatment given every 21 days during 24 months or until progression

Atezolizumab + Tiragolumab + SBRT

Stereotactic body radiation therapy (SBRT) RADIATION

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)

Atezolizumab + Tiragolumab + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years,
• ECOG, Performance status ≤ 1,
• Minimum 3 measurable lesions, with at least one lesion which cannot be irradiated for testing the abscopal effect and at least 2 irradiable lesions.
• Life expectancy \> 6 months,
• At least one non irradiated tumor site that can be biopsied for research purpose,
• Participant must have following advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement:
• Cohort 1 : patient with metastatic non small lung cancer / tumor without oncogenic addiction (EGFR/ALK/ROS/BRAF) which progress after platin based chemotherapy and immunotherapy given as sequential or concomitant therapy.
• Cohort 4 : Head and neck carcinoma / First line locoregional or metastatic recurrence
• Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements Have achieved a complete response, partial response or stable disease and subsequently had disease progression while still on anti-PD-1/L1 therapy Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)
• Adequate hematological, renal, metabolic and hepatic functions:
• Hemoglobin ≥ 9 g/dl (participants may have received prior red blood cell \[RBC\] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 G/l, platelet count ≥ 100 G/l, white blood cell count ≥ 2.5 G/l (or within local laboratory normal limits) and lymphocyte count ≥ 0.75 G/l Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (ASP) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 x ULN in case of extensive skeletal involvement for AP exclusively and ≤ 5 x ULN in case of liver metastasis for AST and ALT).
• Total bilirubin ≤ 1.5 x ULN, (3 x ULN for gilbert disease) Albumin ≥ 25 g/l. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 30 ml/min (according to Cockcroft and Gault formula).
• INR ≤ 1.5 x ULN aPTT ≤ 1.5 X ULN Serum calcium within normal laboratory ranges,
• No prior or concurrent malignant disease if more recent than 3 years
• At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy

You may not qualify if:

• Evidence of symptomatic central nervous system (CNS) or leptomeningeal metastases,
• Women who are pregnant or breast feeding,
• Participation in a study involving a medical or therapeutic intervention in the last 30 days from first treatment administration,
• Previous enrolment in the present study,
• Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
• Known hypersensitivity to any involved study drug or of its formulation components,
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
• Any of the following cardiac criteria:
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2,
• Individuals deprived of liberty or placed under legal guardianship, curatorship or judicial protection.
• Prior organ transplantation, including allogeneic stem cell transplantation,
• Known clinically significant liver disease, including, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease, active viral with positive viralDNA detection.
• History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
• History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy.
• Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible, Participants with controlled Type I diabetes mellitus on a stable insulin regimen are eligible, Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with only dermatologic manifestations \<10% of the skin (e.g., participants with psoriatic arthritis would be excluded) are eligible.

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead

Study Sites (1)

Centre Georges François Leclerc (CGFL)

Dijon, Bourgogne-Franche-Comté, 21000, France

RECRUITING

Related Publications (1)

• Roussot N, Fumet JD, Limagne E, Thibaudin M, Hervieu A, Hennequin A, Zanetta S, Dalens L, Fourrier T, Galland L, Jacob P, Bertaut A, Rederstorff E, Chevalier C, Ghirardi S, Gilbert E, Khoukaz A, Martin E, Nicolet C, Quivrin M, Thibouw D, Vulquin N, Truc G, Rouffiac M, Ghiringhelli F, Mirjolet C. A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. BMC Cancer. 2023 Nov 9;23(1):1080. doi: 10.1186/s12885-023-11534-6.

  PMID: 37946136 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms; Carcinoma, Renal Cell; Head and Neck Neoplasms; Neoplasms

Interventions

atezolizumab; Tiragolumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Kidney Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

François FG GHIRINGHELLI, Professor

CONTACT

03.80.73.77.76; FGhiringhelli@cgfl.fr

Céline CM MIRJOLET, PhD

CONTACT

03.80.73.75.00 poste 80.75; CMirjolet@cgfl.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 28, 2022
• Study Start: December 5, 2022
• Primary Completion: December 5, 2024
• Study Completion: December 5, 2024
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

FR (1)