SELINEXOR for Advanced soft-tissue sarcoma | Leiomyosarcoma | Malignant peripheral nerve sheath tumor

Inclusion criteria

• {"criterion_text":"- Phase II: 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 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- Phase II: Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.\n- Phase II: 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 effective contraceptive method.\n- Phase II: Age: 18-80 years.\n- Phase II: Histologic diagnosis of soft tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) confirmed by central pathology review prior to enrollment with an archive tumor sample. A fresh paraffin embedded tumor tissue block must be provided for all subjects for biomarker analysis before and (when feasible) after treatment with investigational products.\n- Phase II:Metastatic/advanced disease in progression in the last 6 months.\n- Phase II:Patients have previously received at least one previous line of systemic therapy.\n- Phase II: Measurable disease according to RECIST 1.1 criteria.\n- Phase II: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.\n- Phase II:Adequate hepatic, renal, cardiac, and hematologic function.\n- Phase II: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"}

Exclusion criteria

• {"criterion_text":"- Phase II: Three or more systemic treatment lines (including both chemotherapy and targeted therapy) for advanced disease (localized unresectable or metastatic).\n- Phase II: Life expectancy of less than 3 months.\n- Phase II: Major surgery within 4 weeks prior to C1D1.\n- Phase II: Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.\n- Phase II: 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- Phase II: 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- Phase II: Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible).\n- Phase II: Patients who have received any other anti-cancer therapy or investigational product in the last 21 days prior to enrollment.\n- Phase II: 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 5 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.\n- Phase II: Prior selinexor or another XPO1 inhibitor treatment.\n- Phase II: Administration of a previous gemcitabine-containing treatment.\n- Phase II: 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- Phase II: 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- Phase II: Pregnant or breastfeeding females.\n- Phase II: Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois(25) or Mosteller(26) method."}

Primary endpoints

• {"endpoint_text":"- Phase I:Based on Dose Limiting Toxicities (DLTs) observed during first cycle (day 1-21).","definition_or_measurement_approach":"DLTs observed during the first cycle (day 1-21) will be used to determine the MTD or recommended phase II dose."}
• {"endpoint_text":"- Phase II: Progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since the first dose of experimental treatment until month 6 after treatment initiation.","definition_or_measurement_approach":"PFSR at 6 months according to RECIST 1.1: percentage of patients without progression or death from first dose until month 6."}

Secondary endpoints

• {"endpoint_text":"- Phase I: Safety profile of the experimental treatment, through assessment of adverse event type,incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE 5.0","definition_or_measurement_approach":"AE type, incidence, severity, timing, related causes, physical exams and labs; toxicity graded per CTCAE v5.0."}
• {"endpoint_text":"- Phase I: Overall Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 criteria).","definition_or_measurement_approach":"ORR per RECIST 1.1: proportion of subjects with BOR of CR or PR among response-evaluable subjects."}
• {"endpoint_text":"- Phase I:Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression.","definition_or_measurement_approach":"Tumor response assessed per Choi criteria using baseline target lesion identification and follow-up until progression."}
• {"endpoint_text":"- Phase I: Quality of life will be measured with EORTC QLQ-C30.","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 instrument."}
• {"endpoint_text":"- Phase II: Overall survival (OS): OS is defined as the time between the date of first dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.","definition_or_measurement_approach":"Time from first dose to death from any cause; censor at last known alive date."}
• {"endpoint_text":"- Phase II: Overall Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 criteria).","definition_or_measurement_approach":"ORR per RECIST 1.1 as above."}
• {"endpoint_text":"- Phase II: Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression.","definition_or_measurement_approach":"Tumor response per Choi criteria as above."}
• {"endpoint_text":"- Phase II: Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE 5.0.","definition_or_measurement_approach":"AE assessment per CTCAE v5.0 including type, incidence, severity, timing, related causes, labs and exams."}
• {"endpoint_text":"- Phase II:Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.","definition_or_measurement_approach":"Clinical outcomes of post-protocol treatments observed during follow-up."}
• {"endpoint_text":"- Phase II:Quality of life will be measured with EORTC QLQ-C30.","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30."}

Spain

Earliest CTIS Part Ii Submission Date

28-06-2024

Latest Decision Or Authorization Date

02-08-2024

Processing Time Days

35

Number Of Sites

10

Number Of Participants

88

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 code 12; contact email: ensayos@sofpromed.com; phone: 971439900","organisation_type":"Hospital/Clinic/Other health care facility"}