Lymphocyte Support to SBRT in Patients With Oligo-metastatic Solid Cancer
- Conditions
- Interventions
- Registration Number
- NCT06439888
- Lead Sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- 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.
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- 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 ...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 58
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Adult male or female patients (older than 18 years of age at inclusion);
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Histologically or cytologically proven solid cancer at the oligo-metastatic stage amenable to pan-lesion SBRT, as defined by:
- 2 to 5 tumor lesions measurable as per RECIST V1.1 (including primary) with a largest diameter comprised between 1.5 and 5 cm,
- The disease can be either genuinely oligo-metastatic, oligo-progressive, or an induced oligo-metastatic disease,
- All tumor lesions that match criterion I2a must be eligible to SBRT in terms of location and radiotherapy constraints,
- SBRT to all lesions must be feasible over a two-week period,
- Whatever the primary tumor type;
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Patients must agree to comply with biopsy and blood sampling for research purpose;
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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 during the last 4 weeks,
- Immunosuppressive medication during the last 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 during the last 4 weeks,
- Major surgery during the last 4 weeks;
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World Health Organization (WHO) 0 or 1 and Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
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Patients must have adequate organ function defined as follows:
- White blood cell count of equal to or higher than 1,500/mm^3,
- Lymphocyte count of equal to or higher than 800/mm^3,
- Platelet count of equal to or higher than 100,000/mm^3,
- Hemoglobin higher than 9 g/dL,
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal to or less than 2.5 upper level norm (or if liver metastases are present must be equal to or less than 5x upper level norm)
- Serum creatinine clearance higher than 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance;
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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. 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.
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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;
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Patients must be affiliated to a social security system or beneficiary of the same
- Evidence of disease rapidly progressing at the time of screening according to the two last best-fitted imaging modalities (CT-scans, MRI, positron emission tomography), at the discretion of the investigator and the multidisciplinary board (RCP);
- Any evidence of brain metastasis;
- Any situation where irradiation of the target site(s) would imply re-irradiation of a formerly irradiated tumor site;
- Bone metastasis located in a femoral bone if risk of pending fracture is high;
- Liver metastasis adjacent to the stomach or small bowel and liver metastasis that leads to a volume of uninvolved liver less than 700 cc;
- 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;
- Any psychiatric illness or social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
- 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 at least 2 years are eligible;
- 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 tumor necrosis factor-α (TNF-α) blockers. Use of immunosuppressive medications for the management of investigational product-related Adverse Events or in subjects with contrast allergies is acceptable. The use of topical, inhaled and intranasal corticosteroids is permitted;
- Patients with tumor(s) that invade major vessels, as shown unequivocally by imaging studies;
- Patients with central lung metastasis (i.e within 2 cm from hilum) that are cavitary as shown unequivocally by imaging studies;
- Persisting significant toxicities related to prior treatments i.e. Grade 2 and higher adverse event according to CTCAE V5.0 criteria, except for alopecia and biological values defined in inclusion criteria I6;
- Known allergy or hypersensitivity to the study drug. The study drug is contraindicated in patients with soy or peanut allergy;
- Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
- Patients at risk of QT prolongation (including patients with hypokaliemia, baseline QT/corrected QT interval more than 470 ms (for women) and more than 450 ms (for men));
- Pregnant or breastfeeding women;
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acid Stereotactic Body Radiation Therapy 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. Part II : Stereotactic Body Radiation Therapy alone Stereotactic Body Radiation Therapy 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 Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acid all-trans retinoic acid 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. Part I : Stereotactic Body Radiation Therapy + All-trans retinoic acid all-trans retinoic acid 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. Part II : Stereotactic Body Radiation Therapy + All-trans retinoic acid Stereotactic Body Radiation Therapy 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.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicities (DLT) from the first intake to 3 weeks after the treatment initiation 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
Lympho-protective efficacy At 6 weeks after SBRT completion 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))
- Secondary Outcome Measures
Name Time Method Duration of response from 6 weeks to 1 year after SBRT Duration of response
Control rates from 6 weeks to 1 year after SBRT Control rates on the treated lesions
Objective response rate from 6 weeks to 1 year after SBRT Objective response rate
Progression-free survival from 6 weeks to 1 year after SBRT Progression-free survival
Trial Locations
- Locations (2)
Gustave Roussy
🇫🇷Villejuif, France
Centre Léon Bérard
🇫🇷Lyon, France