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

NCT06363773 | Recruiting

• 2 other identifiers: RESTO-IMMUNO2023-A02451-44
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Cancer

Keywords

stereotactic radiotherapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate according to iRECIST criteria at 3 months after stereotactic radiotherapy in patients with confirmed progression after initial response to immunotherapy.

  Assessment of Objective Response Rate (Complete Response and Partial Response with iRECIST criteria) according to a centralised independent reading.

  At 3 months after stereotactic radiotherapy

Secondary Outcomes (13)

• Objective Response Rate according to RECIST 1.1 criteria at 3 months after stereotactic RT in patients with progression after initial response to immunotherapy.

  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.

  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.

  Up to 12 months after stereotactic radiotherapy

• Duration until new systemic treatment start.

  Up to 12 months after stereotactic radiotherapy

• Incidence of Adverse Events (safety)

  Up to 12 months after stereotactic radiotherapy

Study Arms (1)

Stereotactic radiotherapy

EXPERIMENTAL

Patients will perform stereotactic radiotherapy with 3 sessions (8 Gy) during 20 minutes each and with 72 hours in-between, alongside anti-PD1 immunotherapy.

Radiation: Stereotactic Radiotherapy

Interventions

Stereotactic Radiotherapy RADIATION

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 radiotherapy (treatment plan).

Stereotactic radiotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Patient having received previous radiotherapy since the start of immunotherapy,
• 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,
• Pregnant or breast-feeding women,
• Patient under legal protection.

Sponsors & Collaborators

• Elsan: lead

Study Sites (1)

Centre Clinical

Soyaux, Charente, 16800, France

RECRUITING

Related Publications (12)

• 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 Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

  PMID: 26412456 RESULT

• 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 RESULT

• 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 RESULT

• 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):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

  PMID: 26028407 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.

  PMID: 28271869 RESULT

• Hatten SJ Jr, Lehrer EJ, Liao J, Sha CM, Trifiletti DM, Siva S, McBride SM, Palma D, Holder SL, Zaorsky NG. A Patient-Level Data Meta-analysis of the Abscopal Effect. Adv Radiat Oncol. 2022 Mar 3;7(3):100909. doi: 10.1016/j.adro.2022.100909. eCollection 2022 May-Jun.

  PMID: 35372719 RESULT

• Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017 Jun 9;8:15618. doi: 10.1038/ncomms15618.

  PMID: 28598415 RESULT

• Yasmin-Karim S, Ziberi B, Wirtz J, Bih N, Moreau M, Guthier R, Ainsworth V, Hesser J, Makrigiorgos GM, Chuong MD, Wei X, Nguyen PL, Ngwa W. Boosting the Abscopal Effect Using Immunogenic Biomaterials With Varying Radiation Therapy Field Sizes. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):475-486. doi: 10.1016/j.ijrobp.2021.09.010. Epub 2021 Sep 13.

  PMID: 34530092 RESULT

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Vincent ATALLAH, Dr

CONTACT

05 45 69 68 32; vincentatallah298@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot, exploratory, prospective, monocentric study

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 12, 2024
• Study Start: January 27, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

FR (1)