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

Inclusion Criteria26

• 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
• 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)
• 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.
• Participants are not eligible for enrolment in the study if ANY of the following criteria applies:
• 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).