Clinical Trial of Cirtuvivint 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

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Apr 2025 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the progression-free survival rate (PFSR) at 3 months.

Secondary objectives 5

1. To evaluate the safety profile.
2. To evaluate the overall response rate (ORR).
3. To evaluate quality of life.
4. To evaluate median progression-free survival (mPFS).
5. To evaluate median overall survival (mOS).

Conditions and MedDRA coding

Selected Advanced Soft-Tissue Sarcomas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 the 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: 16-70 years.
3. Patients with a diagnosis of advanced unresectable soft-tissue sarcoma and not candidates for surgical rescue including only the following subtypes: solitary fibrous tumor (SFT), synovial sarcoma, clear cell sarcoma, extraskeletal myxoid chondrosarcoma (EMC), alveolar soft part sarcoma, myxoid liposarcoma, desmoid tumor and Ewing´s sarcoma.
4. Metastatic/locally advanced with recent progression (<6 months).
5. Patients should have received at least anthracyclines previously unless not indicated (SFT).
6. Measurable disease according to RECIST 1.1 criteria.
7. Patients must be willing to provide consent for the provision of mandatory biological samples for central pathology review (tumor sample from the three months prior to the start of treatment if the patient has not received any systemic therapy) and translational study (tumor blocks and blood).
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
9. Adequate hepatic, renal, cardiac, and hematologic function.
10. 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
11. Left ventricular ejection fraction ≥50% by echocardiogram or MUGA scan.
12. 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 highly effective contraceptive method.
13. Subjects must be willing to avoid extensive sun exposure, phototherapy, and use of a tanning salon during trial participation.

Exclusion criteria 21

1. Previous treatment with CLK inhibitors.
2. Patients who have received any other anti-cancer therapy or investigational product in the last 28 days prior to enrollment.
3. Four or more systemic therapy lines for advanced disease.
4. Sarcoma subtypes other than the specified in the inclusion criteria.
5. 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 3 years prior to enrollment. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
6. 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. 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. Pregnant or breastfeeding females.
9. Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois (33) or Mosteller (34) method.
10. Life expectancy of less than 3 months.
11. Major surgery within 28 days prior to C1D1.
12. Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or dysfunction that could interfere with absorption of study treatment.
13. 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. 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. Subjects with a corrected QT interval (QTc) using Fridericia’s formula (QTcF) > CTCAE v5.0 Grade 1 (>480 msec) based on the mean of triplicate evaluation at screening. In subjects with ventricular paced rhythm, a 50 msec subtraction should be applied to the QTc to calculate the QTcF, potential exceptions for subjects with pacemakers should be discussed with the Medical Monitor.
16. Subjects with clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), ventricular fibrillation (VF), second or third degree heart block.
17. Subjects with myocardial infarction (MI) within 1 year, Class II-IV congestive heart failure (CHF) per New York Heart Association (NYHA) classification, or clinically significant coronary artery disease (CAD).
18. Subjects currently using or anticipating the need for food or drugs known to strongly inhibit or induce CYP3A4, such as ketoconazole, itraconazole, erythromycin, or rifampin, within 10 days prior to first dose of study medication.
19. Subjects with retinal abnormalities, specifically diabetic retinopathy, macular degeneration, other forms of retinal degenerative disease, or other retinal findings that may place the subject at risk (the latter should be discussed with the Medical Monitor).
20. Subjects with known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
21. Unwilling to participate in the translational study (not providing mandatory written consent for biopsy at baseline).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFSR-3m (according to central radiology assessment): Efficacy measured by the PFSR at 3 months, which is defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 or death due to any cause since the date of treatment initiation until month 3 after date of treatment initiation.

Secondary endpoints 5

1. Safety and tolerability will be assessed by adverse events detected through physical examinations and laboratory tests and graded according to CTCAE v5.0.
2. Overall response rate (ORR) (according to central and local assessment): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).
3. Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.
4. Median progression-free survival (mPFS) (according to central radiology assessment): Efficacy measured by mPFS, which is defined as the median of time in months from date of treatment initiation to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.
5. Median overall survival (mOS): Efficacy measured by an estimation of mOS, which is defined as the median of time in months from date of treatment initiation to date of death due to any cause. OS will be censored on the last date a patient was known to be alive.

Investigational products

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

Test 1

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

Nadia Hindi

Public contact point

Organisation

Asociacion Europea Y Latinoamericana SELNET Para La Investigacion En Sarcomas

Contact name

Nadia Hindi

Third parties 1

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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