Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma (SeliSarc)

January 22, 2024 updated by: Grupo Espanol de Investigacion en Sarcomas

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

Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Phase I-II, randomized, open-label, multicenter, international clinical trial Patients with advanced soft-tissue sarcoma (undifferentiated pleomorphic sarcoma, leiomyosarcoma, alveolar soft-part sarcoma) and osteosarcoma will receive selinexor in combination with gemcitabine.

In the Phase I part safety and toxicity of the combination will be assessed using a 3+3 design. The recommended dose for the Phase II will be determined.

In the Phase II part there will be 4 different cohorts:

Cohort 1: Undifferentiated pleomorphic sarcoma (UPS) Cohort 2: Leiomyosarcoma (LMS) Cohort 3: Alveolar soft-part sarcoma (ASPS) Cohort 4: Osteosarcoma Patients will be randomized for phase II part only (except in cohort 3) in an open-label way to receive selinexor in combination with gemcitabine versus gemcitabine alone

Study Type

Interventional

Enrollment (Estimated)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain, 08025
        • Active, not recruiting
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08035
      • Madrid, Spain, 28046
      • Madrid, Spain, 28040
      • Madrid, Spain, 28040
        • Recruiting
        • H. Fundación Jimenez Díaz
        • Contact:
        • Principal Investigator:
          • Javier Martín Broto, MD
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Universitario Miguel Servet
        • Contact:
        • Contact:
          • Javier Martínez Trufero, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Selinexor + Gemcitabine

Dose escalation levels (Phase I):

All included patients will take both drugs:

Selinexor weekly (given on days 1,8 and 15 of each cycle) will be dispensed at different dose levels: dose level 1:60 mg, dose level 2: 60 mg, dose level 3: 60 mg, and dose level 4: 80 mg).

Gemcitabine weekly (given on days 1, 8 of each cycle) will be administered at different dose levels: (dose level 1:1000 mg/m2 (30 min), dose level 2:1000 mg/m2 (10 mg/m2/min), dose level 3:1200 mg/m2 (10 mg/m2/min) and dose level 4: 1200 mg/m2 (10 mg/m2/min)).

Selinexor: tablet (20 mg tablets) Oral use.

Gemcitabine: Concentrate for solution for infusion. Intravenous use.
Drug: Selinexor
For both interventional ( Selinexor and Gencitabine) Dose-limiting toxicity (DLT) will be applied only to either of the following toxicities occurring during the first treatment cycle (days 1-21).
Other Names:
  • Gemcitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 6 months
To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Selinexor plus gemcitabine.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety profile according to CTCAE 5.0.
Time Frame: 6 months
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.
6 months
Objective response rate (ORR).
Time Frame: 6 months
Objective 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).
6 months
Evaluate efficacy according to Choi response
Time Frame: 6 months
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.
6 months
Patients's quality of life (QoL)
Time Frame: 6 months
Quality of life will be measured with European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire 30
6 months
Pharmacokinetic values in blood analysis
Time Frame: 6 months
Impact of pharmacokinetics. interactions between selinexor in gemcitabine
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Espanol de Investigacion en Sarcomas

Investigators

  • Study Director: Javier Martín Broto, MD, Hospital Fundacion Jimenez Diaz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 2, 2020

Primary Completion (Estimated)

November 30, 2025

Study Completion (Estimated)

May 31, 2026

Study Registration Dates

First Submitted

October 8, 2020

First Submitted That Met QC Criteria

October 20, 2020

First Posted (Actual)

October 22, 2020

Study Record Updates

Last Update Posted (Actual)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEIS-67
  • 2019-000652-33 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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