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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04595994
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : November 17, 2021
Information provided by (Responsible Party):
Grupo Espanol de Investigacion en Sarcomas

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Sarcoma,Soft Tissue Drug: Selinexor Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: unique arms for each possible dose
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : July 1, 2024

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 Name: Gemcitabine

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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

  5. Pharmacokinetic values in blood analysis [ Time Frame: 6 months ]
    Impact of pharmacokinetics. interactions between selinexor in gemcitabine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04595994

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Contact: Guiomar Rodriguez Beloso +34 971 439 900
Contact: Margalida Frau +34 971 439 900

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Hospital de la Santa Creu i Sant Pau Active, not recruiting
Barcelona, Spain, 08025
HU Vall d'Hebron Active, not recruiting
Barcelona, Spain, 08035
H. Fundación Jiménez Díaz Recruiting
Madrid, Spain, 28040
Contact: Javier Martín Broto, MD   
Principal Investigator: Javier Martín Broto, MD         
Hospital Clínico San Carlos Recruiting
Madrid, Spain, 28040
Contact: Antonio Casado, MD   
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Andrés Redondo, MD   
Hospital Universitario Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Javier Martínez Trufero, MD         
Sponsors and Collaborators
Grupo Espanol de Investigacion en Sarcomas
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Study Director: Javier Martín Broto, MD Hospitales Universitarios Virgen del Rocío
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Responsible Party: Grupo Espanol de Investigacion en Sarcomas Identifier: NCT04595994    
Other Study ID Numbers: GEIS-67
First Posted: October 22, 2020    Key Record Dates
Last Update Posted: November 17, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs