A Study to Assess the Ability of Stereotactic Radiotherapy to Restore the Efficacy of Immunotherapy in Patients With Metastatic Cancer.

Official title

Pilot, Exploratory, Prospective Study to Assess the Ability of Stereotactic Radiotherapy to Restore the Efficacy of Anti-PD1 Immunotherapy in Initially Long-responder Patients With Metastatic Progression.

Overview

This study aims at enrolling patients with solid tumors at metastatic stage, considered long responders to immunotherapy (\> 6 months) and displaying disease progression. In this study, the investigator wants to evaluate specific modalities of stereotactic radiotherapy, with 3 sessions, each of 8 Gy, lasting 20 minutes and spaced 72 hours apart (Day 1, Day 4, Day 7). The radiotherapy device itself is not the subject of this study and will be used in accordance with its CE mark and indications. The objective of the study is to assess the ability of stereotactic radiotherapy to restore the lost efficacy of immunotherapy. In particular, the abscopal effect will be assessed, i.e. the action of irradiating a particular target lesion and observing an effect on other distant metastases.

Interventions

• Radiation Stereotactic Radiotherapy
  Patients will perform stereotactic radiotherapy with 3 sessions (8 Gy) during 20 minutes each and with 72 hours in-between. Patients enrolled in the study would not have received this stereotactic radiotherapy outside the study, that is why this procedure is additional (compared to Standard of care) and considered as burdensome (as this is radiation). Before performing the stereotactic radiotherapy, patients will do a radiotherapy CT scanner (no injected) in order to prepare precisely the radio

Primary outcome measures

• Objective Response Rate according to iRECIST criteria at 3 months after stereotactic radiotherapy in patients with confirmed progression after initial response to immunotherapy. [Time frame: At 3 months after stereotactic radiotherapy]

Secondary outcome measures (12)

• Objective Response Rate according to RECIST 1.1 criteria at 3 months after stereotactic RT in patients with progression after initial response to immunotherapy. [Time frame: At 3 months after stereotactic radiotherapy]
• Objective Response Rate according to iRECIST criteria up to 12 months after stereotactic radiotherapy in patients with confirmed progression after initial response to immunotherapy. [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to RECIST 1.1 criteria up to 12 months after stereotactic radiotherapy in patients with confirmed progression after initial response to immunotherapy. [Time frame: Up to 12 months after stereotactic radiotherapy]
• Duration until new systemic treatment start. [Time frame: Up to 12 months after stereotactic radiotherapy]
• Incidence of Adverse Events (safety) [Time frame: Up to 12 months after stereotactic radiotherapy]
• Progression-Free Survival [Time frame: Up to 12 months after stereotactic radiotherapy]
• Overall Survival [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to iRECIST criteria on the irradiated lesion only. [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to RECIST 1.1 criteria on the irradiated lesion only. [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to iRECIST criteria on all untreated lesion(s) (abscopal effect). [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to RECIST 1.1 criteria on all untreated lesion(s) (abscopal effect). [Time frame: Up to 12 months after stereotactic radiotherapy]
• Objective Response Rate according to iRECIST criteria on each untreated lesion taken independently from others (abscopal effect). [Time frame: Up to 12 months after stereotactic radiotherapy]

Eligibility criteria

Inclusion criteria

• Male or female, 18 years of age or older,
• Patient with a metastatic solid tumor,
• Patient with at least one target lesion (for radiotherapy) together with other secondary lesions that must be measurable,
• Measurable disease according to RECIST 1.1 and iRECIST criteria,
• Patient undergoing anti-PD1 immunotherapy as part of standard of care treatment,
• Disease progression with immunotherapy (progression assessed by iRECIST criteria) but having received at least 6 months of immunotherapy,
• Performance Status (PS) of 0 or 1,
• Patient eligible for stereotactic radiotherapy,
• Patient affiliated to or benefiting from a social security scheme,
• Patient having been informed of the investigation and having signed the informed consent form prior to any study-specific procedures,
• Patient willing and able to undergo all examinations and procedures in accordance with the clinical investigation plan.

Exclusion criteria

• Patient having received previous radiotherapy since the start of immunotherapy,
• Patient for whom first disease progression (pre-inclusion stage) is not confirmed secondarily (inclusion stage),
• Patient with an active implantable medical device (e.g. pacemaker) or an active medical device worn on the body that could interact adversely with stereotactic radiotherapy treatment,
• Patient with hematological cancer,
• Symptomatic patient requiring a rapid change of systemic line according to the investigator's judgment,
• Concurrent participation in another clinical trial, or patient having received an investigational product within 30 days prior to inclusion,
• Pregnant or breast-feeding women,
• Patient under legal protection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Centre Clinical — Soyaux

Publications

• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cance PMID 26412456
• Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25. PMID 19706802
• Doyen J, Besse B, Texier M, Bonnet N, Levy A. PD-1 iNhibitor and chemotherapy with concurrent IRradiation at VAried tumor sites in advanced Non-small cell lung cAncer: the Prospective Randomized Phase 3 NIRVANA-Lung Trial. Clin Lung Cancer. 2022 May;23(3):e252-e256. doi: 10.1016/j.cllc.2021.10.008. Epub 2021 Oct 24. PMID 34810130
• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123 PMID 26028407
• Funck-Brentano E, Baghad B, Fort M, Aouidad I, Roger A, Beauchet A, Otmezguine Y, Blom A, Longvert C, Boru B, Saiag P. Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy. Int J Cancer. 2020 Sep 15;147(6):1707-1714. doi: 10.1002/ijc.32934. Epub 2020 Feb 28. PMID 32083739
• Levy A, Khalifa J, Martin E, Botticella A, Quevrin C, Lavaud P, Aldea M, Besse B, Planchard D, Barlesi F, Deutsch E, Massabeau C, Doyen J, Le Pechoux C. Stereotactic body radiotherapy for extra-cranial oligoprogressive or oligorecurrent small-cell lung cancer. Clin Transl Radiat Oncol. 2023 May 3;41:100637. doi: 10.1016/j.ctro.2023.100637. eCollection 2023 Jul. PMID 37206411
• Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018 May;18(5):313-322. doi: 10.1038/nrc.2018.6. Epub 2018 Feb 16. PMID 29449659
• Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824. PMID 22397654

Identifiers

NCT: NCT06363773 · RESTO-IMMUNO · 2023-A02451-44

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗