Lymphocyte Support to SBRT in Patients With Oligo-metastatic Solid Cancer

NCT06439888 | Recruiting Phase 1 DMC

• 2 other identifiers: 2022-500680-13-002022/3511
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to assess safety of pan-metastases directed SBRT combined with ATRA and the lympho-protective efficacy of ATRA upon radiation-induced lymphopenia. This is a French bicentric, open label, phase I/II clinical study that will comprise two parts. Part I will evaluate the safety of the combination based on a single-arm safety run design, while Part II will be randomized (ratio 1:1) and will study SBRT with or without ATRA. Patients enrolled will be treated with:

• SBRT to all lesions more than 1cm, on week days (from Monday to Friday), over a maximum of 2 weeks,
• With or without (for part II patients randomized in the control arm) ATRA therapy: ATRA 150 mg/m\^2/day for 3 days every 3 weeks for a maximum of 4 cycles (about 3 months), starting on the first day of radiation therapy. The expected rate of patients who will have lymphopenia of grade 2 or higher in the control arm at 6 weeks post-radiotherapy is 50%. At a one-sided level of statistical significance of 0.07, the randomization of 52 patients (26 patients in each arm) will provide 85% power to detect a decrease in this rate to 15% in the SBRT+ATRA arm, using Fisher's exact test.

Conditions

Oligometastatic Disease; Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLT)

  Dose-limiting toxicity (DLT) is defined as an adverse event reported during the first three weeks of treatment that is possibly related to study intervention and fulfills any one of the DLT criteria using CTCAE Version 5.0

  from the first intake to 3 weeks after the treatment initiation

• Lympho-protective efficacy

  Rate of patients with lymphopenia grade 2 or higher at 6 weeks after treatment completion (as absolute lymphocyte count less than 800/mm3 (CTCAE V5.0))

  At 6 weeks after SBRT completion

Secondary Outcomes (4)

• Control rates

  from 6 weeks to 1 year after SBRT

• Objective response rate

  from 6 weeks to 1 year after SBRT

• Duration of response

  from 6 weeks to 1 year after SBRT

• Progression-free survival

  from 6 weeks to 1 year after SBRT

Study Arms (3)

Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acid

EXPERIMENTAL

Part I will allow to evaluate the safety of pan-metastases directed SBRT combined with ATRA in N=6 patients. * SBRT to all lesions more than 1.5cm, on Monday up to Friday, over a maximum of 2 weeks, * ATRA 150 mg/m2/day given orally for 3 days every 3 weeks for a maximum of 4 cycles (about 3 months), starting on the same day as SBRT.

Drug: all-trans retinoic acid; Radiation: Stereotactic Body Radiation Therapy

Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acid

EXPERIMENTAL

Part II will allow to evaluate the lympho-protective efficacy of ATRA upon radiation-induced lymphopenia. The experimental arm consists in : * SBRT to all lesions more than 1.5cm, on Monday up to Friday, over a maximum of 2 weeks, * ATRA 150 mg/m2/day given orally for 3 days every 3 weeks for a maximum of 4 cycles (about 3 months), starting on the same day as SBRT.

Drug: all-trans retinoic acid; Radiation: Stereotactic Body Radiation Therapy

Part II : Stereotactic Body Radiation Therapy alone

PLACEBO COMPARATOR

Part II will allow to evaluate the lympho-protective efficacy of ATRA upon radiation-induced lymphopenia. The control arm consists in : \- SBRT to all lesions more than 1.5cm, on Monday up to Friday, over a maximum of 2 weeks

Radiation: Stereotactic Body Radiation Therapy

Interventions

all-trans retinoic acid DRUG

per os treatment, started from the same day as SBRT, during 3 successive days, every 3 weeks, for a maximum of 4 cycles

Also known as: Tretinoin, VESANOID

Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acid; Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acid

Stereotactic Body Radiation Therapy RADIATION

Standard of Care, planned over 1 or 2 weeks, every lesions must be irradiated

Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acid; Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acid; Part II : Stereotactic Body Radiation Therapy alone

Eligibility Criteria

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

You may qualify if:

• Participants are eligible for enrolment in the study only if ALL of the following criteria apply:
• I2. Histologically or cytologically proven solid cancer at the oligometastatic stage and/or oligoprogressive amenable to pan-lesion SBRT, as defined by:
• \[1-5\] active tumor lesions with a largest diameter comprised between \[1-5\] cm,
• The disease can be either genuinely oligometastatic, oligoprogressive, or an induced oligometastatic disease
• All active tumor lesions (progressive and/or hypermetabolic) that match criterion I2a must be eligible to SBRT in terms of location and radiotherapy constraints. 'Active lesion' is defined as either: hypermetabolic on PET-scan, recent increase of \>20% of its largest diameter on CT-scan, and/or any new lesion of ≥ 1cm on the most recent CT-scan
• SBRT to all active lesions must be feasible over a two-week period,
• Whatever the primary tumor type I3. Patients must agree to comply with biopsy and blood sampling for research purpose;
• I4. Minimal wash-out periods from last administration of treatments to the first day of SBRT must be:
• Systemic chemotherapy including cytotoxic, immunotherapy, targeted therapy, hormone therapy, any investigational agent \> 4 weeks,
• Immunosuppressive medication \> 4 weeks, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceeding 10 mg/day of prednisone, or an equivalent corticosteroid,
• Live attenuated vaccination \> 4 weeks,
• Major surgery \> 4 weeks; I5. WHO 0-1 and ECOG Performance Status 0-1;
• I6. Patients must have adequate organ function defined as follows:
• White blood cell count of ≥ 1,500/mm3,
• Lymphocyte count of ≥ 800/mm3,

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (2)

Centre Léon Bérard

Lyon, 69000, France

NOT YET RECRUITING

Gustave Roussy

Villejuif, 94800, France

RECRUITING

MeSH Terms

Interventions

Tretinoin; Radiosurgery

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Eric DEUTSCH, PhD, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa SCHMIDT, MSc

CONTACT

+33 (0)1 42 11 42 11; lisa.schmidt@gustaveroussy.fr

Daphné MOREL, PharmD

CONTACT

+33 (0)1 42 11 42 11; daphne.morel@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 3, 2024
• Study Start: July 11, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)