Trabectedin Maintenance Post 1st-line in STS

NCT ID: NCT02929394

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-07
• Study Completion Date: 2020-06-05

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.

Conditions

Sarcoma, Soft Tissue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

investigational treatment

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.

Group Type: ACTIVE_COMPARATOR

Trabectedin

Intervention Type: DRUG

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

observation

Observation through clinical and radiological follow-up until disease progression (RECIST 1.1).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Yondelis

Eligibility Criteria

Inclusion Criteria

• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
• Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
• Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment.and until 3 months after the last study treatment.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Important note: All eligibility criteria must be adhered to, in case of deviation discussion with Headquarters and study coordinator is mandatory.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Gelderblom

Role: STUDY_CHAIR

Leiden University Medical Centre

Locations

Institut Bergonie

Bordeaux, , France

Centre Oscar Lambret

Lille, , France

Centre Leon Berard

Lyon, , France

Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone

Marseille, , France

Institut Curie

Paris, , France

Gustave Roussy

Villejuif, , France

Medizinische Hochschule Hannover

Hanover, , Germany

UniversitaetsMedizin Mannheim

Mannheim, , Germany

Leiden University Medical Center

Leiden, , Netherlands

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, , Poland

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Barcelona, , Spain

Hospital Universitario San Carlos

Madrid, , Spain

Royal Marsden Hospital - Chelsea, London

London, , United Kingdom

Countries

France; Germany; Netherlands; Poland; Spain; United Kingdom

Other Identifiers

2016-003535-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-1447-STBSG

Identifier Type: -

Identifier Source: org_study_id