Combination treatment of selinexor and gemcitabine for advanced soft-tissue sarcoma

Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas

This study is testing if a new combination of two drugs, selinexor and gemcitabine, can help people with advanced soft-tissue sarcoma feel better and improve their treatment results.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Asociación Europea y Latinoamericana SELNET para la Investigación en Sarcomas (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 11 sites (Santa Cruz de Tenerife, Canary Islands and 10 other locations)
• Trial ID: NCT06114004 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of selinexor combined with gemcitabine in patients with advanced soft-tissue sarcoma, specifically targeting leiomyosarcoma and malignant peripheral nerve sheath tumors. The study is structured in two phases: the first phase assesses safety and toxicity using a 3+3 design, while the second phase includes two cohorts focusing on the specific types of sarcoma. Participants will receive the treatment and undergo follow-up assessments to determine the recommended dose and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with a confirmed diagnosis of advanced leiomyosarcoma or malignant peripheral nerve sheath tumor.

Not a fit: Patients with other types of soft-tissue sarcoma or those whose disease is not metastatic or has not progressed in the last 6 months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced soft-tissue sarcoma.

How similar studies have performed: While this approach is being explored in this specific context, similar combinations of targeted therapies and chemotherapy have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Age: 18-80 years.
3. 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.
4. Metastatic/advanced disease in progression in the last 6 months.
5. Patients have previously received at least one previous line of systemic therapy.
6. Measurable disease according to RECIST 1.1 criteria.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
8. Adequate hepatic, renal, cardiac, and hematologic function.
9. 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 10. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.

11\. 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.

Exclusion Criteria:

1. Three or more systemic treatment lines (including both chemotherapy and targeted therapy) for advanced disease (localized unresectable or metastatic).
2. Patients who have received any other anti-cancer therapy or investigational product in the last 21 days prior to enrollment.
3. 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.
4. Prior selinexor or another XPO1 inhibitor treatment.
5. Administration of a previous gemcitabine-containing treatment.
6. 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.
7. 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.
8. Pregnant or breastfeeding females.
9. Body surface area (BSA) \<1.4 m2 at baseline, calculated by the Du Bois(25) or Mosteller(26) method.
10. Life expectancy of less than 3 months.
11. Major surgery within 4 weeks prior to C1D1.
12. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
13. 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).
14. 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. 15. Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible)
15. Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible)

Where this trial is running

Santa Cruz de Tenerife, Canary Islands and 10 other locations

• Hospital Universitario de Canarias — Santa Cruz de Tenerife, Canary Islands, Spain (Not_yet_recruiting)
• Hospital de la Santa Creu i Sant Pau — Barcelona, Spain (Recruiting)
• Hospital Universitario Vall d'Hebron — Barcelona, Spain (Recruiting)
• Hospital Universitario de Donostia — Donostia / San Sebastian, Spain (Not_yet_recruiting)
• Hospital General Universitario Gregorio Marañón — Madrid, Spain (Not_yet_recruiting)
• Hospital Clínico San Carlos — Madrid, Spain (Recruiting)
• Hospital Universitario Fundación Jiménez Díaz — Madrid, Spain (Recruiting)
• Hospital Universitario La Paz — Madrid, Spain (Recruiting)
• Hospital Clínico Universitario Virgen de la Arrixaca — Murcia, Spain (Not_yet_recruiting)
• Hospital Clinico Universitario Valencia — Valencia, Spain (Not_yet_recruiting)
• Hospital Universitario Miguel Servet — Zaragoza, Spain (Recruiting)

Study contacts

• Study coordinator: Patricio Ledesma

Conditions Sarcoma,Soft Tissue