Phase II Study of Lurbinectedin and Irinotecan in Adult and Young Adult Patients With Advanced Desmoplastic Small Round Cell Tumor (DSRCT)
Patients participating in this study have DSRCT that has spread locally or to other parts of the body and can no longer be surgically removed without causing significant harm. Treatment will continue until the tumor progresses further, severe side effects occur, or either patient or investigator decision. In addition, patients may participate in an optional biological study. The study will analyze the tumor's genes and the molecules related to them. By studying genes and their products, the investigators can better understand the behavior of the tumor and how the body responds to therapies.
• Histological centrally confirmed diagnosis of DSRCT with the documented presence of EWSR1-WT1 translocation.
• Age ≥ 15 years.
• Locally advanced (i.e. radical surgical resection of local disease unfeasible or surgery declined by the patient or surgery deemed to become less demolitive and / or easier after cytoreduction) and/or metastatic disease.
• Measurable disease by RECIST v1.1.
• Clinical or objective disease progression after the last administration of the last standard therapy, or have stopped standard therapy due to intolerability within 6 months from enrollment.
• At least one prior chemotherapy based on anthracycline (considering chemotherapy administered for primary tumour) and no more than 3 prior chemotherapy lines.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
• Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the trial), defined as the following:
∙ platelet count ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL, white blood cells ≥ 3.0 × 109/L and absolute neutrophil count (ANC) ≥ 2.0 × 109/L,
‣ aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN), even in the presence of liver metastases,
‣ total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN,
‣ International Normalized Ratio (INR) \< 1.5 (except if patient is on oral anticoagulation therapy),
‣ calculated creatinine clearance (CrCL) ≥ 30 mL/minute (using Cockcroft-Gault formula),
‣ creatine phosphokinase (CPK) ≤ 2.5 × ULN,
‣ albumin ≥ 3.0 g/dL.
• Cardiac ejection fraction ≥50% as measured by echocardiogram.
⁃ Recovery to grade ≤ 1 or to baseline from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or fatigue grade ≤ 2).
⁃ No history of arterial and/or venous thromboembolic event within the previous 12 months.
⁃ Females of childbearing potential must have a negative pregnancy test (preferable by serum or, if serum test unavailable, urine beta-HCG) within 7 days before treatment start.
⁃ Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
⁃ Male and female patients of reproductive potential must agree to employ a highly effective method of birth control (Acceptable methods of contraception are described in Appendix 5) throughout the study and thereafter, at the end of study treatment, and for at least 7 months from the patient's last lurbinectedin administration in female patients of childbearing potential and for at least 4 months in men in fertile age after the last lurbinectedin administration.
⁃ The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.