Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04595994
Other study ID # GEIS-67
Secondary ID 2019-000652-33
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 2, 2020
Est. completion date May 31, 2026

Study information

Verified date January 2024
Source Grupo Espanol de Investigacion en Sarcomas
Contact Patricio Ledesma
Phone 971 439 900
Email ensayos@sofpromed.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 14
Est. completion date May 31, 2026
Est. primary completion date November 30, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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).

Locations

Country Name City State
Spain Hospital de la Santa Creu i Sant Pau Barcelona
Spain HU Vall d'Hebron Barcelona
Spain H. Fundación Jiménez Díaz Madrid
Spain Hospital Clínico San Carlos Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital Universitario Miguel Servet Zaragoza

Sponsors (1)

Lead Sponsor Collaborator
Grupo Espanol de Investigacion en Sarcomas

Country where clinical trial is conducted

Spain, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Safety profile according to CTCAE 5.0. 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
Secondary Objective response rate (ORR). 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
Secondary Evaluate efficacy according to Choi response 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
Secondary Patients's quality of life (QoL) Quality of life will be measured with European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire 30 6 months
Secondary Pharmacokinetic values in blood analysis Impact of pharmacokinetics. interactions between selinexor in gemcitabine 6 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04577014 - Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma Phase 1/Phase 2
Recruiting NCT06114004 - Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma (SeliSarc) Phase 2
Completed NCT01949506 - (SBRT) and (ART) for Pulmonary Metastases From Soft Tissue Sarcomas N/A
Recruiting NCT05235100 - Preoperative IMRT With Concurrent Apatinib for Localised Extremity or Trunk Sarcoma Phase 2
Completed NCT04991883 - Analysis of the Molecular Profile of the Mixofibrosarcoma of the Extremities
Recruiting NCT04122872 - GISAR German Interdisciplinary Sarcoma Registry
Recruiting NCT04910126 - Camrelizumab Plus Doxorubicin for the First Line Treatment of Adcanced Soft Tissue Sarcoma Phase 2
Recruiting NCT04219202 - Neoadjuvant Irradiation of Retroperitoneal Soft Tissue Sarcoma With Ions Retro-Ion N/A
Recruiting NCT04028479 - The Registry of Oncology Outcomes Associated With Testing and Treatment
Recruiting NCT05886634 - A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma Phase 2
Recruiting NCT05167994 - Preoperative IMRT With Concurrent Anlotinib for Localised Extremity or Trunk Sarcoma Phase 2
Recruiting NCT04673942 - A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors Phase 2
Recruiting NCT05813327 - Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma Phase 1/Phase 2
Recruiting NCT04172805 - Anlotinib Combined With Toripalimab in Refractory and Advanced Soft-tissue Sarcoma Phase 2
Active, not recruiting NCT04887298 - Study of Liposomal Annamycin for the Treatment of Subjects With Soft-Tissue Sarcomas (STS) With Pulmonary Metastases Phase 1/Phase 2
Active, not recruiting NCT03600649 - Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas Phase 1
Recruiting NCT05894018 - Brachytherapy (Iodine-125 Seeds) and Fluzoparib Combination Therapy for Advanced Unresectable Soft Tissue Sarcoma Phase 2
Recruiting NCT06263231 - A Study to Investigate Efficacy & Safety of INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3) Phase 3
Completed NCT01985295 - Combined Modality Treatment of Sarcomas of the Extremities Phase 1
Recruiting NCT05614375 - Endoscopic Surgery in the Treatment of Soft Tissue Sarcoma in Nasal and Paranasal Sinus