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

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ClinicalTrials.gov Identifier: NCT04595994
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Investigacion en Sarcomas

Tracking Information
First Submitted Date  ICMJE October 8, 2020
First Posted Date  ICMJE October 22, 2020
Last Update Posted Date July 8, 2021
Actual Study Start Date  ICMJE September 2, 2020
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
  • 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.
  • 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).
  • 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.
  • 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
  • Pharmacokinetic values in blood analysis [ Time Frame: 6 months ]
    Impact of pharmacokinetics. interactions between selinexor in gemcitabine
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
Official Title  ICMJE Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
unique arms for each possible dose
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sarcoma,Soft Tissue
Intervention  ICMJE 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
Study Arms  ICMJE 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.

Intervention: Drug: Selinexor
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 20, 2020)
14
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2024
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Guiomar Rodriguez Beloso +34 971 439 900 grodriguez@sofpromed.com
Contact: Margalida Frau +34 971 439 900 mfrau@sofpromed.com
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04595994
Other Study ID Numbers  ICMJE GEIS-67
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Grupo Espanol de Investigacion en Sarcomas
Study Sponsor  ICMJE Grupo Espanol de Investigacion en Sarcomas
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Javier Martín Broto, MD Hospitales Universitarios Virgen del Rocío
PRS Account Grupo Espanol de Investigacion en Sarcomas
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP