Clinical trial of selinexor plus gemcitabine in selected advanced soft-tissue sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-08-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514827-40-00

EudraCT number

2019-000652-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Phase I: To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of selinexor plus gemcitabine.
Phase II: Evaluar la eficacia de la combinación de selinexor más gemcitabina medida por la tasa de supervivencia libre de progresión (TSLP) a los 6 meses en pacientes con sarcoma de partes blandas avanzados.

Secondary objectives 10

1. Phase I: To evaluate the safety profile according to CTCAE 5.0.
2. Phase I:To determine the overall response rate (ORR).
3. Phase I: To evaluate efficacy according to Choi response.
4. Phase I:To evaluate the patients’s quality of life (QoL).
5. Phase II:To evaluate overall survival (OS).
6. Phase II:To determine the overall response rate (ORR).
7. Phase II:To evaluate efficacy according to Choi response.
8. Phase II:To evaluate the safety profile according to CTCAE 5.0.
9. Phase II: To evaluate the outcome of post protocol treatments.
10. Phase II: To evaluate the patients’s quality of life (QoL)

Conditions and MedDRA coding

Patients with advanced soft-tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) will receive selinexor in combination with gemcitabine.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Phase II: 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. Phase II: Age: 18-80 years.
3. Phase II: Histologic diagnosis of soft tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) confirmed by central pathology review prior to enrollment 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. Phase II:Metastatic/advanced disease in progression in the last 6 months.
5. Phase II:Patients have previously received at least one previous line of systemic therapy.
6. Phase II: Measurable disease according to RECIST 1.1 criteria.
7. Phase II: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
8. Phase II:Adequate hepatic, renal, cardiac, and hematologic function.
9. Phase II: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. Phase II: Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
11. Phase II: 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 15

1. Phase II: Three or more systemic treatment lines (including both chemotherapy and targeted therapy) for advanced disease (localized unresectable or metastatic).
2. Phase II: Patients who have received any other anti-cancer therapy or investigational product in the last 21 days prior to enrollment.
3. Phase II: Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer, adequately treated cervical carcinoma in situ, superficial bladder carcinoma) during the 5 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
4. Phase II: Prior selinexor or another XPO1 inhibitor treatment.
5. Phase II: Administration of a previous gemcitabine-containing treatment.
6. Phase II: 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.
7. Phase II: 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.
8. Phase II: Pregnant or breastfeeding females.
9. Phase II: Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois(25) or Mosteller(26) method.
10. Phase II: Life expectancy of less than 3 months.
11. Phase II: Major surgery within 4 weeks prior to C1D1.
12. Phase II: Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
13. Phase II: 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).
14. Phase II: 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.
15. Phase II: Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I:Based on Dose Limiting Toxicities (DLTs) observed during first cycle (day 1-21).
2. Phase II: Progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since the first dose of experimental treatment until month 6 after treatment initiation.

Secondary endpoints 10

1. Phase I: 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. Toxicity will be graded and tabulated by using CTCAE 5.0
2. Phase I: Overall 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. Phase I: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. Phase I: Quality of life will be measured with EORTC QLQ-C30.
5. Phase II: Overall survival (OS): OS is defined as the time between the date of first dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
6. Phase II: Overall 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).
7. Phase II: 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.
8. Phase II: 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. Toxicity will be graded and tabulated by using CTCAE 5.0.
9. Phase II:Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.
10. Phase II:Quality of life will be measured with EORTC QLQ-C30.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Sponsor organisation

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Address

Calle De La Sierra De Pajarejo 5 5a

City

Madrid

Postcode

28023

Country

Spain

Scientific contact point

Organisation

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Contact name

Javier Martin

Public contact point

Organisation

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Contact name

Javier Martin

Third parties 1

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications