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Trabectedin Maintenance Post 1st-line in STS

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ClinicalTrials.gov Identifier: NCT02929394
Recruitment Status : Terminated (Poor accrual)
First Posted : October 11, 2016
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
PharmaMar
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Sarcoma, Soft Tissue Drug: Trabectedin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Maintenance Therapy With Trabectedin Versus Observation After First Line Treatment With Doxorubicin of Patients With Advanced or Metastatic Soft Tissue Sarcoma.
Actual Study Start Date : November 7, 2017
Actual Primary Completion Date : June 5, 2020
Actual Study Completion Date : June 5, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Trabectedin

Arm Intervention/treatment
Active Comparator: 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.
Drug: 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
Other Name: Yondelis

No Intervention: observation
Observation through clinical and radiological follow-up until disease progression (RECIST 1.1).



Primary Outcome Measures :
  1. progression-free survival [ Time Frame: 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 :
  1. Safety and tolerability (Common Toxicity Criteria CTCAE 4.0) [ Time Frame: until 3/4 years after randomization of the first patient ]
  2. Overall survival [ Time Frame: until 3/4 years after randomization of the first patient ]
  3. Time to second progression (PFS2) [ Time Frame: until 3/4 years after randomization of the first patient ]
  4. Health related quality of life (QLQ-C30) [ Time Frame: until 3/4 years after randomization of the first patient ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02929394


Locations
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France
Institut Bergonie
Bordeaux, France, 33076
Centre Oscar Lambret
Lille, France, 59020
Centre Leon Berard
Lyon, France, 69008
Assistance Publique - Hopitaux de Marseille - Hôpital de La Timone
Marseille, France, 13385
Institut Curie
Paris, France, 75248
Gustave Roussy
Villejuif, France, 94805
Germany
Medizinische Hochschule Hannover
Hannover, Germany, 30625
UniversitaetsMedizin Mannheim
Mannheim, Germany, 68167
Netherlands
Leiden University Medical Center
Leiden, Netherlands
Poland
Maria Sklodowska-Curie Memorial Cancer Centre
Warsaw, Poland, 02 781
Spain
Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals
Barcelona, Spain, 08907
Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
Barcelona, Spain, 08916
Hospital Universitario San Carlos
Madrid, Spain, 28040
United Kingdom
Royal Marsden Hospital - Chelsea, London
London, United Kingdom, SW3 6JJ
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
PharmaMar
Investigators
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Study Chair: Hans Gelderblom Leiden University Medical Centre
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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT02929394    
Other Study ID Numbers: EORTC-1447-STBSG
2016-003535-38 ( EudraCT Number )
First Posted: October 11, 2016    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All publications must comply with the terms specified in the EORTC Policy 009 "Release of Results and Publication Policy".

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
Histologically proven locally advanced or metastatic high grade STS (excluding histologies insensitive to chemotherapy such as ASPS, PECOMA subtypes)
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents