Combination of Selinexor and Gemcitabine for Advanced Sarcomas

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

This study is testing if combining selinexor with gemcitabine can help people with advanced soft-tissue sarcoma and osteosarcoma feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Grupo Espanol de Investigacion en Sarcomas (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 6 sites (Barcelona and 5 other locations)
• Trial ID: NCT04595994 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 and osteosarcoma. It is a Phase I-II, randomized, open-label, multicenter, international study. The Phase I portion will assess the safety and toxicity of the drug combination, while the Phase II portion will involve four cohorts of patients receiving either the combination treatment or gemcitabine alone. The trial aims to determine the recommended dose and potential benefits of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with confirmed advanced soft-tissue sarcoma or osteosarcoma.

Not a fit: Patients with early-stage sarcoma or those who have not progressed to advanced disease 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 and osteosarcoma.

How similar studies have performed: While there have been studies on sarcoma treatments, the specific combination of selinexor and gemcitabine in this context is relatively novel.

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 (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft part sarcoma) or osteosarcoma 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 previous lines of chemotherapy
2. Prior selinexor or another XPO1 inhibitor treatment.
3. Administration of a previous gemcitabine-containing treatment.
4. 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.
5. 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.
6. Pregnant or breastfeeding females.
7. Body surface area (BSA) \<1.4 m2 at baseline, calculated by the Du Bois(31) or osteller(32) method.
8. Life expectancy of less than 3 months.
9. Major surgery within 4 weeks prior to C1D1.
10. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
11. 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).
12. 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.
13. 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

Barcelona and 5 other locations

• Hospital de la Santa Creu i Sant Pau — Barcelona, Spain (Active_not_recruiting)
• HU Vall d'Hebron — Barcelona, Spain (Recruiting)
• H. Fundación Jiménez Díaz — Madrid, Spain (Recruiting)
• Hospital Clínico San Carlos — Madrid, Spain (Recruiting)
• Hospital Universitario La Paz — Madrid, Spain (Recruiting)
• Hospital Universitario Miguel Servet — Zaragoza, Spain (Recruiting)

Study contacts

• Study coordinator: Patricio Ledesma

Conditions Sarcoma,Soft Tissue