Trabectedin Maintenance Post 1st-line in STS

Phase 3

Terminated

• Conditions: Sarcoma, Soft Tissue
• Interventions: Drug: Trabectedin

• Registration Number: NCT02929394
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

Maintenance therapy with trabectedin versus observation after first line treatment with doxorubicin of patients with advanced or metastatic soft tissue sarcoma.

This is a prospective, multicenter, randomized, open label Phase III trial investigating whether a maintenance treatment with trabectedin, as compared to the observational approach, can prolong progression-free survival in patients with advanced, inoperable and/or metastatic STS after response or stabilisation during first line treatment with doxorubicin.

Detailed Description

Progression free survival will be estimated by the Kaplan-Meier method. The median survival time and its associated 95% non-parametric CI will be provided. Rates at 3 month intervals will be estimated using the log-log transformation of the Kaplan-Meier estimates and the standard deviation of the Kaplan Meier estimate based on the Greenwood formula.

For the primary analysis, PFS from randomization will be compared between the two arms using the score test from a Cox proportional hazards model adjusted for histology (stratification factor). The corresponding estimate of the treatment effect (hazard ratio) and 95% CI will be provided.

Secondary analyses include:

* the primary comparison of PFS repeated using methods for interval-censored data to adjust for deviations from the planned imaging scheduled, if any.

* the above mentioned analyses performed for PFS measured from date of starting firstline doxorubicin treatment.

Overall survival and time to second progression (PFS2) measured from randomization and from starting firstline doxorubicin treatment will be estimated by the Kaplan-Meier method. The median times and their associated 95% non-parametric CI will be calculated. Rates at 3 month intervals will be estimated using the log-log transformation of the Kaplan-Meier estimates and the standard deviation of the Kaplan Meier estimate based on the Greenwood formula. They will be compared between the two arms using an adjusted Cox proportional hazards model; the corresponding estimates of the hazard ratio and 95% CI will be provided. The above mentioned PFS2 comparison will also be repeated using methods for interval-censored data.

The adverse events related to the treatment (excluding those declared not reasonably possibly related to the treatment, but including those with relationship not assessable) will be described in the safety population. Worst grade of the AEs will be tabulated. Whenever a CTCAE code exists, the grade will be displayed according to that system, otherwise the values will be coded in up to three categories as below lower limit of normal (LLN), within normal range, and above upper limit of normal (ULN), as deemed appropriate.

The percentage of patients presenting severe treatment-related AE (grade ≥ 3), of patients reported to have died of toxicity and of patients who stopped treatment due to toxicity will be calculated and the 95% confidence interval will be presented.

Study Timeline

• Study First Submitted: 2016-10-07
• Study First Submitted QC: 2016-10-07
• Study First Posted: 2016-10-11
• Study Start: 2017-11-07
• Status Verified: 2019-11
• Primary Completion: 2020-06-05
• Study Completion: 2020-06-05
• Last Update Submitted: 2020-09-01
• Last Update Posted: 2020-09-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
investigational treatment	Trabectedin	Trabectedin 1.2 mg/m² through a central venous catheter as an IV infusion over 24 hours every 4 weeks until disease progression (RECIST 1.1) or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
progression-free survival	until 3/4 years after randomization of the first patient	The primary end-point is progression-free survival defined from randomization according to RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability (Common Toxicity Criteria CTCAE 4.0)	until 3/4 years after randomization of the first patient
Overall survival	until 3/4 years after randomization of the first patient
Health related quality of life (QLQ-C30)	until 3/4 years after randomization of the first patient
Time to second progression (PFS2)	until 3/4 years after randomization of the first patient

Trial Locations

Locations (14)

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Leon Berard; 🇫🇷 Lyon, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Gustave Roussy; 🇫🇷 Villejuif, France

UniversitaetsMedizin Mannheim; 🇩🇪 Mannheim, Germany

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia); 🇪🇸 Barcelona, Spain

Hospital Universitario San Carlos; 🇪🇸 Madrid, Spain

Maria Sklodowska-Curie Memorial Cancer Centre; 🇵🇱 Warsaw, Poland

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone; 🇫🇷 Marseille, France

Institut Curie; 🇫🇷 Paris, France

Royal Marsden Hospital - Chelsea, London; 🇬🇧 London, United Kingdom

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands