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Metastatic Non Small Cell Lung CancerPhase 1IMMUNOs-SBRTNCT05259319

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)

A Phase 1 study testing Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ], Tiragolumab and Stereotactic body radiation therapy (SBRT) in people with Metastatic Non Small Cell Lung Cancer and Metastatic Bladder Cancer, run by Centre Georges Francois Leclerc at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ], Tiragolumab and Stereotactic body radiation therapy (SBRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteFrance
Study dates
5 Dec 2022to 5 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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 2 : Bladder cancer / Patient with progression following platin based therapy or without maintenance with anti PD1/PD-L1. Patient have to recieve Enfortumab Vedotin before inclusion if the treatment is available. Unless indication by the investigator Cohort 3 : Renal cell carcinoma / Second-line therapy after an anti-angiogenic plus immunotherapy or immunotherapy.
  • 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
  • Criteria to confirm inclusion:
  • At least 2 mesurable lesions should be able to receveid 3 X 8 Gy by SBRT according to the dose constraints to organs at risk (OAR) imposed by the protocol
  • In case of lesion previously treated by radiotherapy, the constraints on the organs at risk must be respected after having summed up the treatment plans.
  • Confirmation of 3 measureable lesions, with at least one lesion which cannot be irradiated for testing the abscopal effect and at least 2 irradiable lesions. Those lesions must be uni-dimensionally ≥ 10 mm considered as measurable according to RECIST v1.1

Who cannot join

  • 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,
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  • History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
  • Treatment with systemic immunosuppressive medications including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to inclusion. Systemic corticosteroids is not allowed but at physiologic doses meaning less than 10 mg/day of prednisone or its equivalent. The use of inhaled corticosteroids and mineral corticoids is allowed.
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days before pre inclusion,
  • Any of the following cardiac criteria:
  • Congestive heart failure ≥ New York Heart Association (NYHA) class 2,
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), Myocardial infarction less than 6 months before pre-inclusion Uncontrolled cardiac arrhythmias, Known left ventricular ejection fraction (LVEF) <50%
  • 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.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L).
  • Severe infections within 2 weeks prior to inclusion, including but not limited to SARS-Cov-2 infection, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to pre-inclusion. Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Any contraindication to tumor biopsy,
  • Participant with spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >2 weeks prior to pre-inclusion.
  • Administration of a live, attenuated vaccine within 4 weeks before the start of study medication or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination is allowed during influenza season only (approximatively October to March).
  • Patient with a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS),
  • Patients with EBV infection (Positive EBV viral capsid antigen IgM test at screening)
  • Active tuberculosis
  • Concomitant use of prohibited concomitant therapy (cf paragraph 6.5.2.2) or anticipation that such concomitant medication/therapies will be required during the study
  • For NSCLC indication, patients with lymphoepithelioma-like carcinoma are excluded.

Trial locations and contacts

1 site in 1 country.

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

France1 site, 1 recruiting
  • Centre Georges François Leclerc (CGFL)

    Dijon, Bourgogne-Franche-Comté, 21000

    François FG GHIRINGHELLI, Professor, 03.80.73.77.76, FGhiringhelli@cgfl.fr

    Sophie PARNALLAND, 03 45 34 80 77 ext. +33, sparnalland@cgfl.fr

    Recruiting

Other trials in France

About this study

Official title: An Open-label, Multi-centric, Phase I, Evaluating the Safety and the Efficacy of Combination of Atezolizumab, Tiragolumab and and Stereotactic Body Radiation Therapy in Patients With Oligometastatic Multiorgan (IMMUNOs-SBRT)

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

Read the detailed description

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).

Being tested
Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ], Tiragolumab, Stereotactic body radiation therapy (SBRT)
Keywords
Atezolizumab, Tiragolumab, Cancer, Stereotactic body radiation therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Urinary Bladder Neoplasms, Carcinoma, Renal Cell, Head and Neck Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ]Drug

    Treatment given every 21 days during 24 months or until progression

  • TiragolumabDrug

    Treatment given every 21 days during 24 months or until progression

  • 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)

Study groups in NCT05259319
Study groupRoleWhat they receive
Atezolizumab + Tiragolumab + SBRTExperimentalAtezolizumab + 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.
Receives: Drug: Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ]; Drug: Tiragolumab; Radiation: Stereotactic body radiation therapy (SBRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 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)

  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

    Measured: 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)
  1. 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.

    Measured: During 6 months after inclusion

  2. 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).

    Measured: Throughout the treatment period (24 months)

  3. 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

    Measured: Until the patient dies

  4. 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.

    Measured: 18 weeks after inclusion

  5. 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.

    Measured: Throughout the treatment period (24 months)

  6. Expansion cohort : To evaluate abscopal effect

    Un-irradiated metastasis volume(s) is evaluated from scanner images

    Measured: Throughout the treatment period (24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2022
  2. Study start5 Dec 2022
  3. Primary completion5 Dec 2024 (estimated)
  4. Study completion5 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05259319
Sponsor's protocol ID
2021-003848-25
Acronym
IMMUNOs-SBRT
Status last verified
Oct 2023
First submitted
24 Jan 2022
Last updated
17 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37946136

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab 60 MG/1 ML Intravenous Solution [TECENTRIQ], Tiragolumab and Stereotactic body radiation therapy (SBRT) in people with Metastatic Non Small Cell Lung Cancer and Metastatic Bladder Cancer, run by Centre Georges Francois Leclerc at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact François FG GHIRINGHELLI, Professor (03.80.73.77.76, FGhiringhelli@cgfl.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I : to evaluate safety of SBRT (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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05259319, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2023.

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