Multicohort Trial of Trabectedin and Low-dose Radiation Therapy in Advanced/Metastatic Sarcomas

NCT05131386 | Unknown Phase 2

• 1 other identifier: GEIS-75
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 7

Brief Summary

Phase II, multicohort, single arm, open-label, multicenter, international clinical trial with three cohorts (cohort A: Soft tissue sarcoma, cohort B: Bone tumors (osteosarcoma, chondrosarcoma and cohort C: Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas)) with 7 sites in Spain. Main objective: To evaluate the overall response rate (ORR) in the irradiated nodules according to RECIST v1.1 criteria. Treatment Medication Trabectedin at 1.5 mg/m2 24-h IV CI along with radiation therapy (30 Gy, 3 Gy/day for 10 days for non-extremity location and 45 Gy, 1.8 Gy/day for 25 days for extremity location of target lesion(s)), starting within 1 hour after the first trabectedin infusion withdrawal (day 2)) will be given every 3 weeks up to progression or intolerance. Premedication 4 mg oral dexamethasone 24h and 12h before trabectedin administration, 20 mg IV dexamethasone 30 minutes before treatment. Ondansetron or analogue will also be given prior to trabectedin.

Conditions

Soft Tissue Sarcoma; Bone Tumors; Small Round-cell Sarcomas

Keywords

Osteosarcoma; Chondrosarcoma; Ewing's sarcoma; Rhabdomyosarcoma; Desmoplastic small round-cell tumors

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) in the irradiated nodules

  ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) only in the irradiated nodules divided by the number of response evaluable subjects (according to RECIST v1.1 criteria and based on central radiology review). This is considered a good surrogate for palliative relief.

  6 weeks

Secondary Outcomes (8)

• Overall response rate (ORR) considering all the lesions

  6 weeks

• Progression-free survival rate (PFSR) at 6 months considering all the lesions

  6 months

• Median progression-free survival (mPFS)

  6 months

• Time to progression (TTP) of irradiated nodules

  6 weeks

• Overall survival (OS)

  6 months

Study Arms (1)

Multicohort trial of trabectedin and low-dose radiation therapy in advanced/metastatic sarcomas

EXPERIMENTAL

Premedication 4 mg oral dexamethasone 24h and 12h before trabectedin administration, 20 mg IV dexamethasone 30 minutes before treatment. Ondansetron or analogue will also be given prior to trabectedin. Medication Trabectedin at 1.5 mg/m2 24-h IV CI along with radiation therapy (30 Gy, 3 Gy/day for 10 days for non-extremity location and 45 Gy, 1.8 Gy/day for 25 days for extremity location of target lesion(s)), starting within 1 hour after the first trabectedin infusion withdrawal (day 2)) will be given every 3 weeks up to progression or intolerance.

Drug: Trabectedin

Interventions

Trabectedin DRUG

ET-743, Yondelis (vials of 1 mg). Route of administration: intravenous infusion

Also known as: Yondelis

Multicohort trial of trabectedin and low-dose radiation therapy in advanced/metastatic sarcomas

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must provide written informed consent prior to performance of 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. blood count, imaging tests, etc.) and 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.
• Age: 16-75 years.
• Patients must have a diagnosis of soft tissue sarcoma (cohort A), bone tumors (osteosarcoma, chondrosarcoma) (cohort B) or small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas) (cohort C), with metastasis or locally advanced disease, and not suitable for metastasectomy or surgical resection or not oncologically recommended metastasectomy. A centralized diagnosis will be performed, and the central diagnosis confirmation will be mandatory prior to enrollment (tumor sample must be available and sent during screening).
• Disease distribution allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point, taking into account that the dose for extremities will be 45 Gy while for non-extremity will be 30 Gy.
• Those lesions considered for radiation therapy must be related with a clinically relevant symptom. It is not necessary to irradiate all the lesions within one organ. Irradiating pulmonary lesions with infiltration of pleural serosa should be discouraged.
• Patients must have documentation of disease progression within 6 months prior to study entry.
• The patient must have been considered eligible for systemic chemotherapy. Patients should had received at least one line of systemic therapy (anthracycline-based in the case of Cohort A-STS, unless the patient is not candidate for treatment with anthracyclines), with a maximum of three previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included.
• The following sarcoma types are eligible:
• Soft tissue sarcoma
• Bone tumors (osteosarcoma, chondrosarcoma)
• Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas)
• Measurable disease, according to RECIST v1.1 criteria.
• Performance status ≤ 1 (ECOG).
• Adequate respiratory functions: FEV1 \> 1L; DLCO \> 40% (patients with pulmonary target lesions).
• Adequate bone marrow function (hemoglobin ≥ 9 g/dL, leukocytes ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3). Patients with creatinine clearance (based on Cockroft and Gault) ≥30 ml/min, albumin ≥ 25 g/L, ALT and AST ≤ 2.5 times the ULN, total bilirubin ≤ ULN, CPK ≤ 2.5 times ULN, alkaline phosphatase ≤ 2.5 times the ULN are acceptable. If the increase of alkaline phosphatase is \> 2.5 times the ULN, then the alkaline phosphatase liver fraction and/or GGT must be ≤ ULN.

You may not qualify if:

• Previous treatment with trabectedin or previous treatment with radiotherapy (this latter just in case the previous radiotherapy treatment does not allow the radiotherapy treatment of this study due to tissue constrains).
• Normal tissue constrains for radiation therapy.
• Performance status ≥ 2 (ECOG).
• Plasma bilirubin \> ULN.
• Creatinine clearance \<30ml/min.
• History of other neoplastic disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated or no evidence of recurrence for more than 5 years after primary tumor treatment.
• Severe chronic obstructive pulmonary disease (COPD) or other severe pulmonary diseases.
• Significant cardiovascular disease (for example, dyspnea \> 2 NYHA).
• Significant systemic diseases grade 3 or higher on the NCI-CTCAE v5.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.
• Uncontrolled bacterial, mycotic or viral infections.
• Known positive test for infection by human immunodeficiency virus (HIV).
• Women who are pregnant or breast-feeding.
• Psychological, familiar, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent.
• Patients who have participated in another clinical trial and/or have received any other investigational product in the last 30 days prior to enrollment.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (7)

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, 38320, Spain

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28009, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms; Osteosarcoma; Chondrosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrés Redondo

  Hospital Universitario La Paz

  PRINCIPAL INVESTIGATOR

• Claudia Valverde

  Hospital Universitari Vall d'Hebrón

  PRINCIPAL INVESTIGATOR

• Katarina Majercakova

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

• Josefina Cruz

  Hospital Universitario de Canarias

  PRINCIPAL INVESTIGATOR

• Rosa Álvarez

  Hospital General Universitario Gregorio Marañón

  PRINCIPAL INVESTIGATOR

• Antonio Casado

  Hospital San Carlos, Madrid

  PRINCIPAL INVESTIGATOR

• Javier Martín Broto

  Hospital Universitario Fundación Jiménez Díaz

  STUDY DIRECTOR

Central Study Contacts

Patricio Ledesma

CONTACT

971439900; ensayos@sofpromed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II, multicohort, single arm, open-label, multicenter, international clinical trial

Study Record Dates

• First Submitted: November 11, 2021
• First Posted: November 23, 2021
• Study Start: May 28, 2021
• Primary Completion: July 28, 2024
• Study Completion: July 28, 2024
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7)