Informations générales (source: ClinicalTrials.gov)
Pan-lesions SBRT Combined With Lymphocyte Support Through ATRA-driven Blockade of MDSC in Patients With Oligo-metastatic Solid Cancer
Interventional
Phase 1/Phase 2
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
juillet 2024
janvier 2027
02 décembre 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Eric DEUTSCH | 06/10/2026 19:05:32 | Contacter | ||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Bérard - 69000 - Lyon - France | Gwenaëlle GARIN-FOURNIER, PhD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
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. [1-5] active tumor lesions with a largest diameter comprised between [1-5] cm,
2. The disease can be either genuinely oligometastatic, oligoprogressive, or an induced
oligometastatic disease
3. 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
4. SBRT to all active lesions must be feasible over a two-week period,
5. 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:
1. Systemic chemotherapy including cytotoxic, immunotherapy, targeted therapy, hormone
therapy, any investigational agent > 4 weeks,
2. 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,
3. Live attenuated vaccination > 4 weeks,
4. Major surgery > 4 weeks; I5. WHO 0-1 and ECOG Performance Status 0-1;
I6. Patients must have adequate organ function defined as follows:
1. White blood cell count of ≥ 1,500/mm3,
2. Lymphocyte count of ≥ 800/mm3,
3. Platelet count of ≥ 100,000/mm3,
4. Hemoglobin > 9 g/dL, Serum ALT and AST ≤2.5 ULN (or if liver metastases are present
must be ≤ 5x ULN)
f. 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).
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. [1-5] active tumor lesions with a largest diameter comprised between [1-5] cm,
2. The disease can be either genuinely oligometastatic, oligoprogressive, or an induced
oligometastatic disease
3. 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
4. SBRT to all active lesions must be feasible over a two-week period,
5. 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:
1. Systemic chemotherapy including cytotoxic, immunotherapy, targeted therapy, hormone
therapy, any investigational agent > 4 weeks,
2. 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,
3. Live attenuated vaccination > 4 weeks,
4. Major surgery > 4 weeks; I5. WHO 0-1 and ECOG Performance Status 0-1;
I6. Patients must have adequate organ function defined as follows:
1. White blood cell count of ≥ 1,500/mm3,
2. Lymphocyte count of ≥ 800/mm3,
3. Platelet count of ≥ 100,000/mm3,
4. Hemoglobin > 9 g/dL, Serum ALT and AST ≤2.5 ULN (or if liver metastases are present
must be ≤ 5x ULN)
f. 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).