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

Launched by GUSTAVE ROUSSY, CANCER CAMPUS, GRAND PARIS · May 28, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with oligometastatic solid tumors, which means they have a few cancer spots in different areas of the body, but not widespread cancer. The study aims to determine how safe it is to combine a type of targeted radiation therapy called SBRT with a medication called ATRA, which may help protect the immune system during treatment. The trial is divided into two parts: the first part will focus on safety, while the second part will compare the outcomes of patients receiving both treatments versus those receiving only the radiation therapy.

To participate, patients must be adults over 18 with a specific type of cancer that meets certain criteria, including having 2 to 5 measurable tumor spots. Participants will receive SBRT over a maximum of two weeks, and those in the second part may also receive ATRA for about three months. Patients should be in good overall health and willing to undergo some additional tests. It’s important to know that this trial is currently recruiting participants and aims to provide insights into whether this combination treatment can effectively reduce side effects related to the immune system after radiation.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Adult male or female patients (older than 18 years of age at inclusion);
• * Histologically or cytologically proven solid cancer at the oligo-metastatic stage amenable to pan-lesion SBRT, as defined by:
• • 1. 2 to 5 tumor lesions measurable as per RECIST V1.1 (including primary) with a largest diameter comprised between 1.5 and 5 cm,
• • 2. The disease can be either genuinely oligo-metastatic, oligo-progressive, or an induced oligo-metastatic disease,
• • 3. All tumor lesions that match criterion I2a must be eligible to SBRT in terms of location and radiotherapy constraints,
• • 4. SBRT to all lesions must be feasible over a two-week period,
• • 5. Whatever the primary tumor type;
• • Patients must agree to comply with biopsy and blood sampling for research purpose;
• * 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 during the last 4 weeks,
• • 2. 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,
• • 3. Live attenuated vaccination during the last 4 weeks,
• • 4. Major surgery during the last 4 weeks;
• • World Health Organization (WHO) 0 or 1 and Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
• * Patients must have adequate organ function defined as follows:
• • 1. White blood cell count of equal to or higher than 1,500/mm\^3,
• • 2. Lymphocyte count of equal to or higher than 800/mm\^3,
• • 3. Platelet count of equal to or higher than 100,000/mm\^3,
• • 4. Hemoglobin higher than 9 g/dL,
• • 5. 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)
• • 6. 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;
• • 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.
• • 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;
• • Patients must be affiliated to a social security system or beneficiary of the same
• Exclusion Criteria:
• • 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.