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Oligometastatic DiseasePhase 1/2LySATRANCT06439888

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

A Phase 1/2 study testing all-trans retinoic acid and Stereotactic Body Radiation Therapy in people with Oligometastatic Disease and Solid Tumor, Adult, run by Gustave Roussy, Cancer Campus, Grand Paris at 2 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oligometastatic Disease, Solid Tumor, Adult
What is being tested?
all-trans retinoic acid and Stereotactic Body Radiation Therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
2 sitesFrance
Study dates
11 Jul 2024to Jan 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants are eligible for enrolment in the study only if ALL of the following criteria apply:
  • I1. Adult male or female patients (≥ 18 years of age at inclusion);
  • 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
Show all 28Show fewer
  • 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,
  • Platelet count of ≥ 100,000/mm3,
  • Hemoglobin > 9 g/dL, Serum ALT and AST ≤2.5 ULN (or if liver metastases are present must be ≤ 5x ULN)
  • Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance; I7. Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test within 3 days prior to the initiation of the study drug and/or perform a urine test in addition to the serum test before the first dose of ATRA, if the result of the serum test cannot be obtained within 3 days. Fertile men with a female partner of childbearing potential must agree to use male condom plus spermicide and childbearing potential women must have agreed to use at least one highly effective contraceptive method during treatment on this trial and for up to 1 month after the last dose of ATRA; Pregnancy testing and contraception counseling should be repeated monthly throughout the period of ATRA treatment.
  • I8. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol; I9. Patients must be affiliated to a social security system or beneficiary of the same 4.2. Non-inclusion criteria
  • Participants are not eligible for enrolment in the study if ANY of the following criteria applies:
  • E1. Evidence of disease rapidly progressing at the time of screening according to the two last best-fitted imaging modalities (CT-scans, MRI, PET-scan), at the discretion of the investigator and the multidisciplinary board (RCP); E2. Any evidence of brain metastasis; E3. Any situation where irradiation of the target site(s) would imply re-irradiation of a formerly irradiated tumor site; E4. Bone metastasis located in a femoral bone if risk of pending fracture is high; E5. Liver metastasis adjacent to the stomach or small bowel and liver metastasis that leads to a volume of uninvolved liver < 700 cc; E6. Patients with any concurrent severe condition (grade 3 or beyond according to CTCAE V5.0) and/or uncontrolled medical condition that could compromise participation in the study; E7. Any psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent; E8. Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Sponsor. Examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, and isolated elevation of prostate-specific antigen. Patients with a completely treated prior malignancy who are no longer treated (including maintenance therapy) and no evidence of disease for ≥ 2 years are eligible; E9. Chronic treatment with systemic corticosteroids or another immunosuppressant including, but not limited to systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and TNF-α blockers. Use of immunosuppressive medications for the management of investigational product-related AEs or in subjects with contrast allergies is acceptable. The use of topical, inhaled and intranasal corticosteroids is permitted; E10. Patients with tumor(s) that invade major vessels, as shown unequivocally by imaging studies; E11. Patients with central lung metastasis (i.e within 2 cm from hilum) that are cavitary as shown unequivocally by imaging studies; E12. Persisting significant toxicities related to prior treatments i.e. ≥ Grade 2 adverse event according to CTCAE V5.0 criteria, except for alopecia and biological values defined in inclusion criteria I6; E13. Known allergy or hypersensitivity to the study drug. The study drug is contraindicated in patients with soy or peanut allergy; E14. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); E15. Patients at risk of QT prolongation (including patients with hypokaliemia, baseline QT/QTc interval > 470 ms (for women) and > 450 ms (for men)); E16. Pregnant or breastfeeding women; E17. Persons deprived of their freedom or under guardianship, or for whom it would be impossible to undergo the medical follow-up required by the trial, for geographic, social or psychological reasons.
  • Women of childbearing potential must have a negative serum β-HCG pregnancy test within 3 days prior to the administration of the first study treatment (and/or a urine test).
  • Sexually active women of childbearing potential must agree to use a highly effective method of contraception, or to abstain from sexual activity during the study and for at least 1 months after the last study treatment administration.
  • Sexually active male patients must agree to use condom during the study and for at least 1 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.
  • Of note:
  • A woman is considered of childbearing potential following menarche and until becoming post-menopausal (≥ 12 months of non-therapy-induced amenorrhea) unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral oophorectomy and bilateral salpingectomy.
  • A highly effective birth control method is a one which can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: combined (estrogen and progestogen containing) hormonal contraception; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence during the entire period of risk associated with study treatment. To prevent the risk of interaction between the study drug and hormonal contraceptives, hormonal contraceptives should be supplemented with a barrier method (preferably male condom). Following methods are considered as unacceptable methods (non-exhaustive list): periodic abstinence (calendar, symptothermal, post-ovulation methods) and withdrawal (coitus interruptus).

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

France2 sites, 2 recruiting
  • Centre Léon Bérard

    Lyon, 69000

    Gwenaëlle GARIN-FOURNIER, PhD, +33 (0)4 26 55 68 24, gwenaelle.garin@lyon.unicancer.fr

    Vincent GREGOIRE, PhD, MD

    Not yet recruiting
  • Gustave Roussy

    Villejuif, 94800

    Eric DEUTSCH, PhD, MD, +33 (0)1 42 11 42 11, eric.deutsch@gustaveroussy.fr

    Eric DEUTSCH, PhD, MD

    Recruiting

Other trials in France

About this study

Official title: Pan-lesions SBRT Combined With Lymphocyte Support Through ATRA-driven Blockade of MDSC in Patients With Oligo-metastatic Solid Cancer

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.

Read more

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.

Read the detailed description

Ablative radiotherapy - also called stereotactic body radiation therapy (SBRT) - can achieve durable control of tumor lesions and appears as a highly promising strategy to extend overall survival of patients with oligo-metastatic diseases. Radiotherapy has recognized immunomodulatory effects: it triggers immunogenic cell death and reprogramming of the tumor immune microenvironment, which eventually results in a systemic antitumor response following focal radiation treatment. This is called the abscopal effect (distant out-of-the-field lesions that shrink after focal irradiation). Unfortunately, evidences show that this is directly counteracted by the toxic effects of radiotherapy on cytotoxic lymphocytes, which are highly radiosensitive.

Recent data support the fact that radiation-induced lymphopenia is mostly driven by the deregulation of the myeloid-lymphoid imbalance following radiation therapy, with aberrant myelopoiesis and high levels of tumor infiltration by myeloid-derived suppressive cells (MDSC). In preclinical models, pharmacological blockade of MDSC combined with radiation therapy successfully abrogated radiation-induced lymphopenia and significantly improved survival outcomes.

All trans retinoic acid (ATRA, also known as tretinoin) is a vitamin A derivative that has a market authorization for the treatment of acute promyelocytic leukemia as it efficiently induces differentiation of abnormal promyelocytes. Similarly, several clinical studies report that ATRA can differentiate MDSCs into mature myeloid cells, with a positive effect on the count of activated cluster of differentiation 8 (CD8+) lymphocytes.

This clinical trial will provide the clinical proof-of-concept that adding ATRA to pan-metastases SBRT is safe in humans, prevents severe and prolonged lymphopenia and therefore, may foster a radiation-induced systemic anticancer immune response sufficient to increase survival in patients with cancer at the oligo-metastatic stage.

Being tested
all-trans retinoic acid, Stereotactic Body Radiation Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • all-trans retinoic acidDrug

    Also called Tretinoin, VESANOID

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

  • Stereotactic Body Radiation TherapyRadiation

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

Study groups in NCT06439888
Study groupRoleWhat they receive
Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acidExperimentalPart 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.
Receives: Drug: all-trans retinoic acid; Radiation: Stereotactic Body Radiation Therapy
Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acidExperimentalPart 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.
Receives: Drug: all-trans retinoic acid; Radiation: Stereotactic Body Radiation Therapy
Part II : Stereotactic Body Radiation Therapy alonePlacebo comparatorPart 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
Receives: Radiation: Stereotactic Body Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: from the first intake to 3 weeks after the treatment initiation

  2. 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))

    Measured: At 6 weeks after SBRT completion

Secondary outcomes (4)
  1. Control rates

    Control rates on the treated lesions

    Measured: from 6 weeks to 1 year after SBRT

  2. Objective response rate

    Objective response rate

    Measured: from 6 weeks to 1 year after SBRT

  3. Duration of response

    Duration of response

    Measured: from 6 weeks to 1 year after SBRT

  4. Progression-free survival

    Progression-free survival

    Measured: from 6 weeks to 1 year after SBRT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2024
  2. Study start11 Jul 2024
  3. Primary completionSep 2026 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06439888
Sponsor's protocol ID
2022-500680-13-00
Other IDs
2022/3511
Acronym
LySATRA
Status last verified
Nov 2025
First submitted
28 May 2024
Last updated
1 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing all-trans retinoic acid and Stereotactic Body Radiation Therapy in people with Oligometastatic Disease and Solid Tumor, Adult, run by Gustave Roussy, Cancer Campus, Grand Paris at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lisa SCHMIDT, MSc (+33 (0)1 42 11 42 11, lisa.schmidt@gustaveroussy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (DLT) (time frame: from the first intake to 3 weeks after the treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.

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