Using targeted stereotactic radiotherapy to try to restore immunotherapy response in metastatic cancer

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.

This will try three focused stereotactic radiotherapy sessions (8 Gy each on days 1, 4, and 7) to see if that can restore response to anti‑PD‑1 immunotherapy in people with metastatic solid tumors who began to progress after at least six months on immunotherapy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Elsan (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Soyaux, Charente)
• Trial ID: NCT06363773 on ClinicalTrials.gov

What this trial studies

The trial enrolls adults with metastatic solid tumors who have been on anti‑PD‑1 immunotherapy for six months or more but now show disease progression by iRECIST/RECIST 1.1. Participants receive stereotactic radiotherapy to one target lesion given as three 8 Gy fractions spaced 72 hours apart while continuing standard‑of‑care immunotherapy. The main goal is to see whether local high‑dose radiotherapy can trigger an abscopal effect, producing tumor regression at non‑irradiated metastatic sites. The radiotherapy devices are used according to their CE mark and institutional practice, and outcomes are measured on measurable lesions per RECIST/iRECIST criteria.

Who should consider this trial

Good fit: Adults (≥18) with metastatic solid tumors on anti‑PD‑1 immunotherapy for at least six months who now have documented progression and at least one lesion suitable for stereotactic radiotherapy plus other measurable metastases are eligible.

Not a fit: Patients who are not receiving anti‑PD‑1 therapy, have poor performance status (PS ≥2), lack measurable distant lesions, or cannot tolerate stereotactic radiotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could restore sensitivity to anti‑PD‑1 treatment and produce tumor shrinkage at distant metastases without changing systemic therapy.

How similar studies have performed: Small case series and early‑phase trials have reported occasional abscopal responses when combining radiotherapy with immunotherapy, but results have been inconsistent and not confirmed in large randomized trials.

Eligibility criteria

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.

Where this trial is running

Soyaux, Charente

• Centre Clinical — Soyaux, Charente, France (Recruiting)

Study contacts

• Study coordinator: Vincent ATALLAH, Dr

Conditions Metastatic Cancer; stereotactic radiotherapy; immunotherapy