Phase II study of lurbinectedin and irinotecan in adult and young adult patients with advanced desmoplastic small round cell tumor (DSRCT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Italian Sarcoma Group

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

21 Nov 2025 → ongoing

Decision date (initial)

2025-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pharma Mar S.A. · Rising Tide Foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this study is to explore the activity of lurbinectedin and irinotecan from 2nd to 4th line following prior treatment with anthracyclines-based regimens, in progressive patients aged major or equal 15 years with a histologically and molecularly proven diagnosis of advanced EWSR1-WT1 translocated DSRCT. Therefore, with reference to a population of patients with progressive disease by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1, locally advanced or metastatic, EWSR1-WT1 translocated DSRCT pre- treated with one to three lines of systemic treatment, the primary end-point of the study will be to assess.

Secondary objectives 1

1. Llurbinectedin and irinotecan efficacy will be investigated by means of progression-free survival (PFS), overall survival (OS) and duration of response. The impact of the experimental treatment on patients’ quality of life and safety will be also evaluated

Conditions and MedDRA coding

Desmoplastic small round cell tumor

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Histological centrally confirmed diagnosis of DSRCT with the documented presence of EWSR1-WT1 translocation.
2. Age ≥ 15 years
3. Locally advanced (i.e. radical surgical resection of local disease unfeasible or surgery declined by the patient or surgery deemed to become less demolitive and / or easier after cytoreduction) and/or metastatic disease.
4. Measurable disease by RECIST v1.1
5. Clinical or objective disease progression after the last administration of the last standard therapy, or have stopped standard therapy due to intolerability within 6 months from enrollment.
6. At least one prior chemotherapy based on anthracycline (considering chemotherapy administered for primary tumour) and no more than 3 prior chemotherapy lines.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
8. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the trial), defined as the following: a. platelet count ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL, white blood cells ≥ 3.0 × 109/L and absolute neutrophil count (ANC) ≥ 2.0 × 109/L, b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN), even in the presence of liver metastases, c. total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN, d. International Normalized Ratio (INR) < 1.5 (except if patient is on oral anticoagulation therapy), e. calculated creatinine clearance (CrCL) ≥ 30 mL/minute (using Cockcroft-Gault formula), f. creatine phosphokinase (CPK) ≤ 2.5 × ULN, g. albumin ≥ 3.0 g/dL
9. Cardiac ejection fraction ≥50% as measured by echocardiogram.
10. Recovery to grade ≤ 1 or to baseline from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or fatigue grade ≤ 2).
11. No history of arterial and/or venous thromboembolic event within the previous 12 months.
12. Females of childbearing potential must have a negative pregnancy test (preferable by serum or, if serum test unavailable, urine beta-HCG) within 7 days before treatment start.
13. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential.
14. Male and female patients of reproductive potential must agree to employ a highly effective method of birth control (Acceptable methods of contraception are described in Appendix 5) throughout the study and thereafter, at the end of study treatment, and for at least 7 months from the patient’s last lurbinectedin administration in female patients of childbearing potential and for at least 4 months in men in fertile age after the last lurbinectedin administration.
15. The patient or legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.

Exclusion criteria 24

1. Prior treatment with lurbinectedin or trabectedin, Ecubectedin (PM 14) or PM54.
2. Known hypersensitivity to irinotecan or lurbinectedin or any of their components of the drugs products (excipients)
3. Other primary malignancy with <5 years clinically assessed disease free interval, except basal cell skin cancer, cervical carcinoma in situ or other neoplasm judged to entail a low risk of relapse.
4. History or presence of unstable angina, myocardial infarction, or clinically significant valvular heart disease within 12 months of the study.
5. Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e. congestive heart failure, myocardial infarction within 12 months of study).
6. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment within 12 months of study.
7. Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart).
8. Severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
9. Known active brain metastasis.
10. Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis).
11. Diagnosis of human deficiency virus (HIV), hepatitis C virus (HCV) infection or active hepatitis B (to be excluded during the screening period).
12. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or sub-occlusion or paralysis.
13. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
14. Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study.
15. Known active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
16. Prior bone marrow and/or stem cell transplantation, and allogenic transplant.
17. Last dose of systemic cytotoxic therapy or investigational therapy within 21 days from enrollment.
18. Prior treatment with any form of radiation therapy within 14 days from enrollment.
19. Major surgery within 3 weeks prior to study entry and minor surgery within 1 week prior to study entry.
20. Use of strong inducers of CYP3A activity within two weeks prior to the first infusion of lurbinectedin (Appendix 6).
21. Expected limitation of the patient’s ability to comply with the treatment or follow-up protocol.
22. Subjects who have current active hepatic or biliary disease (with exception of patients with asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment).
23. Subjects who have known Gilbert’s syndrome.
24. Patient has received a live or liver attenuated vaccines within 30 days before the first dose of study intervention. Killed vaccines are allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall tumour Response Rate (ORR), according to RECIST v 1.1

Secondary endpoints 5

1. Overall Survival (OS)
2. Progression Free Survival (PFS)
3. Duration of Response (DoR)
4. Safety (according to CTC-AE v.5)
5. EORTC-QLQ-C30 and brief inventory pain

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Italian Sarcoma Group

Sponsor organisation

Italian Sarcoma Group

Address

Via Luigi Carlo Farini 31

City

Bologna

Postcode

40124

Country

Italy

Scientific contact point

Organisation

Italian Sarcoma Group

Contact name

Silvia Stacchiotti

Public contact point

Organisation

Italian Sarcoma Group

Contact name

Gianluca Ignazzi

Locations

2 EU/EEA countries · 11 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 37 files

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

Application history

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