Phase I-II, non-randomized, single-arm, open-label, multicenter, international clinical trial.
Patients with advanced soft-tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) will receive selinexor in combination with gemcitabine.
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.
Age: 18-80 years.
Histologic diagnosis of soft tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) confirmed by central pathology review prior to enrolment 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.
Metastatic/advanced disease in progression in the last 6 months.
Three or more systemic treatment lines (including both chemotherapy and targeted therapy) for advanced disease (localized unresectable or metastatic).
Patients who have received any other anti-cancer therapy or investigational product in the last 21 days prior to enrollment.
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.
Prior selinexor or another XPO1 inhibitor treatment.
Single group
Selinexor 20 MG
DrugAfter having completed the Phase I part, the recommended dose for Phase II is 60mg Selinexor
Gemcitabine
DrugGemcitabine will be given at the dose 1200 mg/m2 (10 mg/m2/min) days 1 and 8 every 21 days.
progression-free survival rate (PFSR)
To evaluate the efficacy of the selinexor plus gemcitabine combination as measured by the progression-free survival rate (PFSR) at 6 months in patients with selected advanced soft-tissue sarcomas.
Overall survival (OS)
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.
Overall response rate (ORR) according to RECIST 1.1
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.
Evaluate the efficacy according to Choi response
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.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
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.
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