Phase I-II prospective trial, multicenter, open label, exploring the combination of Trabectedin plus RAdiotherapy in Soft Tissue Sarcoma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asoc Grupo Espanol De 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)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518199-30-00

EudraCT number

2014-001549-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the maximum tolerated dose (MTD) or the recommended phase II dose of trabectedin for the combination with radiation therapy. The safety profile for each cohort and dose level of trabectedin will be determined in order to find the recommended dose for phase II part in a specific way for each cohort of treatment. Adverse effects will be collected following the CTCAE 4.03 and they will be used as a rule for escalating or diminishing dose-levels regarding the dose-limiting toxicities detailed within the protocol.
For Phase II the main objective was as follows:
- RECIST response for the combination of trabectedin plus radiation
o
therapy in cohorts A, B.
- CHOI response for the combination of trabectedin plus radiation therapy in cohort C.
- In cohort D to improve 5-year relapse-free survival (RFS), decreasing the 5-year relapse percentage from 30% to 10% in patients with well differentiated liposarcoma with cellular component and dedifferentiated G2 retroperitoneal resected liposarcoma (20% increase in RFS).

Conditions and MedDRA coding

Soft tissue sarcoma patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Inclusion Criteria Cohort C and D 1. The patient must voluntarily sign the informed consent form before performing any study-specific test that is not part of the patient's usual care. 2. Aged between 18 and 75 years. 3. The following histological subtypes may be included in the cohort C: High grade leiomyosarcoma (G2-3), liposarcoma (G2-3), if at least 30% of the tumour is dedifferentiated, pleomorphic liposarcoma. The following histological subtypes may be included in the cohort D: Well differentiated liposarcoma (WD liposarcoma) and G2 dedifferentiated liposarcorcoma, if less than 30% of the tumour is dedifferentiated. A centralised diagnosis will be made to confirm that the patient can be included in the study. 4. The tumour must be located in the retroperitoneum and it must be resectable and without evidence of regional or distal spread after the appropriate staging process. This point must be confirmed by the central surgeon reviewer. 5. The location and size of the disease in the retroperitoneum must allow for compliance with radiotherapy limitations in healthy tissue. This point must be confirmed by the site's radiation oncologist and the central radiation oncologist reviewer. 6. Measurable disease according to CHOI criteria for cohort, and RECIST V 1.1 criteria for cohort D. 7. ECOG performance status 0–1. 8. Adequate haematological parameters (haemoglobin >10 g/dl, leukocytes ≥3,000/mm3, neutrophils ≥1,500/mm3, platelets ≥100,000/mm3). Patients with plasma creatinine ≤1.6 mg/dl, transaminases ≤2.5 times the ULN, total bilirubin ≤ ULN, CPK ≤2.5 times ULN, alkaline phosphatase ≤2.5 times ULN are acceptable. If the increase in alkaline phosphatase is >2.5 times the ULN, the liver fraction of alkaline phosphatase and/or GGT should be ≤ULN. 9. Fertile men or women must use an effective contraceptive method before starting the study, during the study and for 6 months following the conclusion thereof. Women of childbearing potential who participate in the study must undergo a pregnancy test before starting the study. 10. Normal cardiac function with LVEF ≥50% by echocardiogram or MUGA. 11. HBV and HCV serology must be performed before including the patient in the study. If HbsAg is positive, it is advisable to rule out a replicative phase (HbsAg*, DNA HBV+). If positive, the patient's inclusion in the trial is not recommended, and it is at the discretion of the investigator to administer preventive treatment with lamivudine. If a potential patient is positive to anti-HCV antibodies, the presence of the virus will be ruled out with a qualitative PCR, or the patient cannot be included in the study (if the qualitative PCR test cannot be performed on the patient, they cannot be included in the study). 12. Patient may have had one previous chemotherapy line (Only Cohort D). 13. The patient must have a central venous catheter for the administration of the treatment. -- For cohort A abd B please see the protocol--

Exclusion criteria 1

1. Exclusion criteria Cohort C and D: 1. Unresectable tumours. 2. Location other than the retroperitoneum. 3. Patients who have previously received systemic treatment with chemotherapy (trabectedin included). For cohort D, patients may have received one previous line of chemotherapy with any other agent. 4. Patients who underwent prior local treatment for retroperitoneal sarcoma: surgery or radiotherapy in the tumour bed. 5. ECOG performance status ≥2. 6. Presence of metastasis or lymph node involvement of the tumour. 7. Previous history of another neoplastic disease with less than 5 years free of disease except for basal cell carcinoma or properly treated in situ cervical cancer. 8. Significant cardiovascular disease (e.g. dyspnoea >2 NYHA). 9. A significant grade 3 or greater systemic disease on the NCI-CTCAE v4.03 scale, which may limit the availability of the patient or which, in the opinion of the investigator, may contribute to the toxicity caused by the study treatment. 10. Uncontrolled viral, mycotic or bacterial infections. 11. Known HIV-positive patients. 12. Pregnant or breast-feeding women. 13. Psychological, familial, social or geographical circumstances that limit the patient's ability to comply with the protocol or informed consent form. 14. Patients who have participated in another clinical trial and/or have received another investigational product in the 30 days prior to inclusion in the trial. -- For Cohort A and B please see the protocol --

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine the maximum tolerated dose (MTD) or the recommended phase II dose of trabectedin for the combination with radiation therapy. RECIST response for the combination of trabectedin plus radiation therapy in cohorts A, B. CHOI response for the combination of trabectedin plus radiation therapy in cohort C. In cohort D to improve 5-year relapse-free survival (RFS), decreasing the 5-year relapse percentage from 30% to 10% in cohort D patients.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asoc Grupo Espanol De Investigacion En Sarcomas

Sponsor organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Address

Calle Del Conde De Aranda 20 Planta 5 Puerta Derecha

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Elisa Cerezo

Public contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Adriana Rojo

Third parties 1

Locations

3 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Results and documents

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

Documents 19 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