NCT04595994

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
0mo left

Started Sep 2020

Longer than P75 for phase_1

Geographic Reach
1 country

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 2, 2020

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

October 8, 2020

Completed
14 days until next milestone

First Posted

Study publicly available on registry

October 22, 2020

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2025

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2026

Expected
Last Updated

January 23, 2024

Status Verified

January 1, 2024

Enrollment Period

5.2 years

First QC Date

October 8, 2020

Last Update Submit

January 22, 2024

Conditions

Sarcoma,Soft Tissue

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD)

    To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Selinexor plus gemcitabine.

    6 months

Secondary Outcomes (5)

  • Safety profile according to CTCAE 5.0.

    6 months

  • Objective response rate (ORR).

    6 months

  • Evaluate efficacy according to Choi response

    6 months

  • Patients's quality of life (QoL)

    6 months

  • Pharmacokinetic values in blood analysis

    6 months

Study Arms (1)

Selinexor + Gemcitabine

EXPERIMENTAL

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

Interventions

SelinexorDRUG

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).

Also known as: Gemcitabine
Selinexor + Gemcitabine

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Three or more previous lines of chemotherapy
  • Prior selinexor or another XPO1 inhibitor treatment.
  • Administration of a previous gemcitabine-containing treatment.
  • 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.
  • 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.
  • Pregnant or breastfeeding females.
  • Body surface area (BSA) \<1.4 m2 at baseline, calculated by the Du Bois(31) or osteller(32) method.
  • Life expectancy of less than 3 months.
  • Major surgery within 4 weeks prior to C1D1.
  • Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
  • 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).
  • 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.
  • Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

ACTIVE NOT RECRUITING

HU Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

H. Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

Related Publications (4)

  • Kashyap T, Argueta C, Unger T, Klebanov B, Debler S, Senapedis W, Crochiere ML, Lee MS, Kauffman M, Shacham S, Landesman Y. Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents. Oncotarget. 2018 Jul 20;9(56):30773-30786. doi: 10.18632/oncotarget.25637. eCollection 2018 Jul 20.

    PMID: 30112106BACKGROUND

  • Park KS, Han BG, Lee KH, Kim DS, Kim JM, Jeon H, Kim HS, Suh SW, Lee EH, Kim SY, Lee BI. Depletion of nucleophosmin via transglutaminase 2 cross-linking increases drug resistance in cancer cells. Cancer Lett. 2009 Feb 18;274(2):201-7. doi: 10.1016/j.canlet.2008.09.007. Epub 2008 Oct 11.

    PMID: 18851895BACKGROUND

  • Hill R, Rabb M, Madureira PA, Clements D, Gujar SA, Waisman DM, Giacomantonio CA, Lee PW. Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy. Cell Death Dis. 2013 Sep 5;4(9):e791. doi: 10.1038/cddis.2013.307.

    PMID: 24008735BACKGROUND

  • Martin-Broto J, Casado A, Marquina G, Redondo A, Martinez-Trufero J, Valverde C, Gutierrez A, Bernabeu D, Ortega L, Merino J, Ramos R, Ledesma P, Mondaza-Hernandez JL, Moura DS, Hindi N. Gemcitabine plus selinexor in selective advanced sarcomas: a phase I of the Spanish group for research on sarcoma study. Nat Commun. 2026 Jan 20. doi: 10.1038/s41467-026-68729-1. Online ahead of print.

    PMID: 41559089DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

selinexorGemcitabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Javier Martín Broto, MD

    Hospital Fundación Jiménez Díaz

    STUDY DIRECTOR

Central Study Contacts

Patricio Ledesma

CONTACT

971 439 900ensayos@sofpromed.com

Gabriel Joan Viver Llompart

CONTACT

971 439 900gviver@sofpromed.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: unique arms for each possible dose
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 8, 2020

First Posted

October 22, 2020

Study Start

September 2, 2020

Primary Completion

November 30, 2025

Study Completion (Estimated)

May 31, 2026

Last Updated

January 23, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

ES(6)