Trabectedin Maintenance Post 1st-line in STS

NCT02929394 | Terminated Phase 3 DMC

• 2 other identifiers: EORTC-1447-STBSG2016-003535-38
• Study Type: interventional
• Target: 13
• Locations: 6 countries
• Sites: 14

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.

Conditions

Sarcoma, Soft Tissue

Keywords

Histologically proven locally advanced or metastatic high grade STS (excluding histologies insensitive to chemotherapy such as ASPS, PECOMA subtypes)

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  The primary end-point is progression-free survival defined from randomization according to RECIST 1.1.

  until 3/4 years after randomization of the first patient

Secondary Outcomes (4)

• 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

• Time to second progression (PFS2)

  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

Study Arms (2)

investigational treatment

ACTIVE COMPARATOR

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.

Drug: Trabectedin

observation

NO INTERVENTION

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

Interventions

Trabectedin 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

Also known as: Yondelis

investigational treatment

Eligibility Criteria

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

* Histologically proven locally advanced or metastatic high grade STS (excluding histologies insensitive to chemotherapy such as ASPS, PECOMA subtypes) * Non-progressive disease (CR, PR or SD according to RECIST 1.1) after 6 cycles of first-line chemotherapy with doxorubicin for advanced and/or metastatic malignant STS. * Interval from last dose of doxorubicin to start of treatment is maximum 6 weeks. * Prior neoadjuvant or adjuvant non-anthracycline-chemotherapy is allowed, provided that the disease did not progress during neoadjuvant and/or adjuvant therapy or within 12 weeks after completion of the perioperative treatment. * Representative formalin fixed, paraffin embedded tumor blocks or 10 unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial. Age 18 years or older WHO performance status ≤ 1 Adequate bone marrow, liver and renal function and coagulation parameters: * neutrophils ≥ 1.5 x 109/L; * hemoglobin ≥ 9 g/dL (or ≥ 5.6 mmol/L). Blood transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values; * platelets ≥ 100 x 109/L; * Total bilirubin ≤ ULN; * Albumin \> 30g/L * SGPT/ALT and SGOT/AST ≤ 2.5 x ULN for patients with liver metastasis or patients with Gilbert syndrome bilirubin ≤ ULN; * Creatine phosphokinase (CPK) ≤ 2.5 x ULN; * Alkaline phosphatase ≤ 2.5 x ULN (consider hepatic isoenzymes 5-nucleotidase or gamma glutamyl transpeptidase (GGT), if the elevation could be osseous in origin); Creatinine clearance/eGFR \>30mL/minmin as per local standard method * Normal cardiac function (LVEF assessed by MUGA or ECHO within normal range of the institution), normal 12 lead ECG (without clinically significant abnormalities). The following unstable cardiac conditions are not allowed: * Congestive heart failure * Angina pectoris * Myocardial infarction within 1 year before registration/randomization * Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy * Arrhythmias clinically significant * No prior exposure to trabectedin * Recovery from toxicity (no more than Grade 1, except for alopecia) * No active or uncontrolled infections or serious illnesses or medical conditions, including a history of chronic alcohol abuse, hepatitis, HIV and/or cirrhosis. * No active brain metastases (e.g. stable for \<4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy is allowed if administered as stable dose for at least one month before randomization) * No history, within the past five years, of malignancies other than soft tissue sarcoma (except: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score 6 and postoperative PSA \< 0.5 ng/ml). Patients with any history of malignancies who are disease-free for more than 5 years are eligible. * 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• PharmaMar: collaborator

Study Sites (14)

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone

Marseille, 13385, France

Location

Institut Curie

Paris, 75248, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

UniversitaetsMedizin Mannheim

Mannheim, 68167, Germany

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, 02 781, Poland

Location

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

Barcelona, 08907, Spain

Location

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

Barcelona, 08916, Spain

Location

Hospital Universitario San Carlos

Madrid, 28040, Spain

Location

Royal Marsden Hospital - Chelsea, London

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Hans Gelderblom

  Leiden University Medical Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 11, 2016
• Study Start: November 7, 2017
• Primary Completion: June 5, 2020
• Study Completion: June 5, 2020
• Last Updated: September 2, 2020

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); ES (3); FR (6); PL (1); GB (1); NL (1)