CIRTUVIVINT for Advanced soft-tissue sarcoma

Inclusion criteria

• {"criterion_text":"- Patients must provide written informed consent prior to performance of any study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to the start of the screening process. Procedures conducted as part of the patient’s routine clinical management (e.g., imaging tests), obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.\n- Laboratory tests as follows: • Absolute neutrophil count ≥1,500/mm³ • Platelet count ≥100,000/mm³ • Bilirubin ≤1.5 mg/dL • AST and ALT ≤2.5 times upper limit of normal • Creatinine ≤1.5 mg/dL\n- Left ventricular ejection fraction ≥50% by echocardiogram or MUGA scan.\n- Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and agree to use birth control measures during study treatment and for 3 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an highly effective contraceptive method.\n- Subjects must be willing to avoid extensive sun exposure, phototherapy, and use of a tanning salon during trial participation.\n- Age: 16-70 years.\n- Patients with a diagnosis of advanced unresectable soft-tissue sarcoma and not candidates for surgical rescue including only the following subtypes: solitary fibrous tumor (SFT), synovial sarcoma, clear cell sarcoma, extraskeletal myxoid chondrosarcoma (EMC), alveolar soft part sarcoma, myxoid liposarcoma, desmoid tumor and Ewing´s sarcoma.\n- Metastatic/locally advanced with recent progression (<6 months).\n- Patients should have received at least anthracyclines previously unless not indicated (SFT).\n- Measurable disease according to RECIST 1.1 criteria.\n- Patients must be willing to provide consent for the provision of mandatory biological samples for central pathology review (tumor sample from the three months prior to the start of treatment if the patient has not received any systemic therapy) and translational study (tumor blocks and blood).\n- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.\n- Adequate hepatic, renal, cardiac, and hematologic function."}

Exclusion criteria

• {"criterion_text":"- Previous treatment with CLK inhibitors.\n- Life expectancy of less than 3 months.\n- Major surgery within 28 days prior to C1D1.\n- Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.\n- Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the NCCN CPGO for antiemesis and anorexia/cachexia (palliative care).\n- Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.\n- Subjects with a corrected QT interval (QTc) using Fridericia’s formula (QTcF) > CTCAE v5.0 Grade 1 (>480 msec) based on the mean of triplicate evaluation at screening. In subjects with ventricular paced rhythm, a 50 msec subtraction should be applied to the QTc to calculate the QTcF, potential exceptions for subjects with pacemakers should be discussed with the Medical Monitor.\n- Subjects with clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), ventricular fibrillation (VF), second or third degree heart block.\n- Subjects with myocardial infarction (MI) within 1 year, Class II-IV congestive heart failure (CHF) per New York Heart Association (NYHA) classification, or clinically significant coronary artery disease (CAD).\n- Subjects currently using or anticipating the need for food or drugs known to strongly inhibit or induce CYP3A4, such as ketoconazole, itraconazole, erythromycin, or rifampin, within 10 days prior to first dose of study medication.\n- Subjects with retinal abnormalities, specifically diabetic retinopathy, macular degeneration, other forms of retinal degenerative disease, or other retinal findings that may place the subject at risk (the latter should be discussed with the Medical Monitor).\n- Patients who have received any other anti-cancer therapy or investigational product in the last 28 days prior to enrollment.\n- Subjects with known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.\n- Unwilling to participate in the translational study (not providing mandatory written consent for biopsy at baseline).\n- Four or more systemic therapy lines for advanced disease.\n- Sarcoma subtypes other than the specified in the inclusion criteria.\n- Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer, adequately treated cervical carcinoma in situ, superficial bladder carcinoma) during the 3 years prior to enrollment. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.\n- Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.\n- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.\n- Pregnant or breastfeeding females.\n- Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois (33) or Mosteller (34) method."}

Primary endpoints

• {"endpoint_text":"- PFSR-3m (according to central radiology assessment): Efficacy measured by the PFSR at 3 months, which is defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 or death due to any cause since the date of treatment initiation until month 3 after date of treatment initiation.","definition_or_measurement_approach":"Defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 or death due to any cause from treatment initiation until month 3; assessment by central radiology review."}

Secondary endpoints

• {"endpoint_text":"- Safety and tolerability will be assessed by adverse events detected through physical examinations and laboratory tests and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Assessment of adverse events via physical examinations and laboratory tests, graded per CTCAE v5.0."}
• {"endpoint_text":"- Overall response rate (ORR) (according to central and local assessment): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR = number of patients with BOR of CR or PR divided by number of response-evaluable patients; assessments per RECIST v1.1 by central and local review."}
• {"endpoint_text":"- Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"Patient-reported outcomes measured via the EORTC QLQ-C30 instrument."}
• {"endpoint_text":"- Median progression-free survival (mPFS) (according to central radiology assessment): Efficacy measured by mPFS, which is defined as the median of time in months from date of treatment initiation to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.","definition_or_measurement_approach":"mPFS = median time (months) from treatment initiation to radiological progression per RECIST v1.1 or death; assessed by central radiology."}
• {"endpoint_text":"- Median overall survival (mOS): Efficacy measured by an estimation of mOS, which is defined as the median of time in months from date of treatment initiation to date of death due to any cause. OS will be censored on the last date a patient was known to be alive.","definition_or_measurement_approach":"mOS = median time (months) from treatment initiation to death from any cause; censoring at last known alive date."}

Spain

Earliest CTIS Part Ii Submission Date

17-12-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

482

Number Of Sites

9

Number Of Participants

28

Primary sponsor

Full Name

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Sofpromed Investigacion Clinica S.L.","duties_or_roles":"sponsorDuties codes: 1, 12","organisation_type":"Hospital/Clinic/Other health care facility"}