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

Metastatic Cancer Clinical Trial

— RESTO-IMMUNO  

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06363773
• Other study ID #: RESTO-IMMUNO
• Secondary ID: 2023-A02451-44
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Elsan
• Contact: Vincent ATALLAH, Dr
• Phone: 05 45 69 68 32
• Email: vincentatallah298[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 35
• Est. completion date: June 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, 18 years of age or older,

2. Patient with a metastatic solid tumor,

3. Patient with at least one target lesion (for radiotherapy) together with other secondary lesions that must be measurable,

4. Measurable disease according to RECIST 1.1 and iRECIST criteria,

5. Patient undergoing anti-PD1 immunotherapy as part of standard of care treatment,

6. Disease progression with immunotherapy (progression assessed by iRECIST criteria) but having received at least 6 months of immunotherapy,

7. Performance Status (PS) of 0 or 1,

8. Patient eligible for stereotactic radiotherapy,

9. Patient affiliated to or benefiting from a social security scheme,

10. Patient having been informed of the investigation and having signed the informed consent form prior to any study-specific procedures,

11. Patient willing and able to undergo all examinations and procedures in accordance with the clinical investigation plan.

Exclusion Criteria:

1. Patient having received previous radiotherapy since the start of immunotherapy,

2. Patient for whom first disease progression (pre-inclusion stage) is not confirmed secondarily (inclusion stage),

3. 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,

4. Patient with hematological cancer,

5. Symptomatic patient requiring a rapid change of systemic line according to the investigator's judgment,

6. Concurrent participation in another clinical trial, or patient having received an investigational product within 30 days prior to inclusion,

7. Pregnant or breast-feeding women,

8. Patient under legal protection.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis

Intervention

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 radiotherapy (treatment plan).

Locations

Country	Name	City	State
France	Centre Clinical	Soyaux	Charente

Sponsors (1)

Lead Sponsor	Collaborator
Elsan

Country where clinical trial is conducted

France, 

References & 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, — View Citation

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, Harbis — View Citation

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):5379-8 — View Citation

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) — View Citation

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. 202 — View Citation

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 2 — View Citation

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 ca — View Citation

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. — View Citation

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 abscop — View Citation

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 respon — View Citation

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/ncom — View Citation

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 Radia — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective Response Rate according to RECIST 1.1 criteria at 3 months after stereotactic RT in patients with progression after initial response to immunotherapy.	Assessment of Objective Response Rate (Complete Response and Partial Response with RECIST 1.1 criteria) according to a centralised independent reading.	At 3 months after stereotactic radiotherapy
Secondary	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
Secondary	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
Secondary	Duration until new systemic treatment start.	Duration (in days) before introduction of a new systemic treatment.	Up to 12 months after stereotactic radiotherapy
Secondary	Incidence of Adverse Events (safety)	Collection of adverse events (AEs) up to 12 months after radiotherapy.	Up to 12 months after stereotactic radiotherapy
Secondary	Progression-Free Survival		Up to 12 months after stereotactic radiotherapy
Secondary	Overall Survival		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to iRECIST criteria on the irradiated lesion only.		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to RECIST 1.1 criteria on the irradiated lesion only.		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to iRECIST criteria on all untreated lesion(s) (abscopal effect).		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to RECIST 1.1 criteria on all untreated lesion(s) (abscopal effect).		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to iRECIST criteria on each untreated lesion taken independently from others (abscopal effect).		Up to 12 months after stereotactic radiotherapy
Secondary	Objective Response Rate according to RECIST 1.1 criteria on each untreated lesion taken independently from others (abscopal effect).		Up to 12 months after stereotactic radiotherapy