Doxorubicin vs. Trabectedin Plus Doxorubicin in Non Operable and/or Metastatic STS

This study has been terminated.
(Interim analysis did not show good results for main objective)
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Investigacion en Sarcomas
ClinicalTrials.gov Identifier:
NCT01104298
First received: April 13, 2010
Last updated: October 26, 2015
Last verified: October 2015
  Purpose
The proposed investigation intends to explore if the combination of trabectedin and doxorubicin in the first line of treatment of advanced sarcomas obtains better results than doxorubicin monotherapy

Condition Intervention Phase
Sarcoma
Drug: Doxorubicin
Drug: Trabectedin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Open, Multicenter, Prospective, Phase II Clinical Trial of Doxorubicin vs. Trabectedin Plus Doxorubicin in the First Line Treatment of Patients With Advanced Non Operable and/or Metastatic Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by Grupo Espanol de Investigacion en Sarcomas:

Primary Outcome Measures:
  • To determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS) [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS). To this end, progression free survival will be compared between both groups of treatment.


Secondary Outcome Measures:
  • To determine activity by means of RECIST objective responses in both study arms, trabectedin/doxorubicin combination and the control arm. [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To determine activity by means of RECIST objective responses in both study arms, trabectedin/doxorubicin combination and the control arm.

  • To determine the tumor control (response rates plus stabilizations) in both arms of treatment. [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To determine the tumor control (response rates plus stabilizations) in both arms of treatment.

  • Overall survival. [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    Overall survival.

  • To determine activity by tissue changes applying the Choi criteria to Soft Tissue Sarcomas (STS)(see radiological review sub study). [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To determine activity by tissue changes applying the Choi criteria to Soft Tissue Sarcomas (STS)(see radiological review sub study).

  • To determine toxicity of trabectedin/doxorubicin combination and the control arm. [ Time Frame: 2012 ] [ Designated as safety issue: Yes ]
    To determine toxicity of trabectedin/doxorubicin combination and the control arm.

  • To determine protein and mRNA expression of genes possibly involved in a potential profile of more favorable response or resistance to study drugs and to analyze the prognostic impact of them on predefined efficacy parameters. [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To determine protein and mRNA expression of genes possibly involved in a potential profile of more favorable response or resistance to study drugs and to analyze the prognostic impact of them on predefined efficacy parameters.

  • To evaluate genomic instability, as well as protein expression that could influence response/resistance to the study drugs and make a correlation with efficacy endpoints. [ Time Frame: 2012 ] [ Designated as safety issue: No ]
    To evaluate genomic instability, as well as protein expression that could influence response/resistance to the study drugs and make a correlation with efficacy endpoints.


Enrollment: 115
Study Start Date: November 2009
Study Completion Date: May 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A

Classic Doxorubicin (Adriamycin - Doxorubicin hydrochloride) Presentation: Solution with 10, 20, or 50 mg Doxorubicin Hydrochloride. Excipients: hydrochloric acid and sodium chloride 0.9%, q.s. 25 ml.

Pharmaceutical form: concentrate for solution for infusion. Route of administration: Intravenous

Drug: Doxorubicin
A maximum of 6 cycles every 3 weeks of doxorubicin monotherapy 75 mg/square meter will be given in the absence of progression or not acceptable toxicity.
Other Name: Adriamycin
Experimental: Arm B

Trabectedin Presentation: vials with trabectedin 1 mg and sucrose 400 mg. Pharmaceutical form: A white or whitish lyophilized powder as concentrate for solution for injection.

Route of administration: for intravenous use after reconstitution and further dilution.

Classic Doxorubicin (Adriamycin - Doxorubicin hydrochloride) Presentation: Solution with 10, 20, or 50 mg Doxorubicin Hydrochloride. Excipients: hydrochloric acid and sodium chloride 0.9%, q.s. 25 ml.

Pharmaceutical form: concentrate for solution for infusion. Route of administration: Intravenous

Drug: Trabectedin
A maximum of 6 cycles every 3 weeks of the combination (Trabectedin 1,1 mg/square meter + doxorubicin 60 mg/square meter) will be given in the absence of progression or not acceptable toxicity.
Other Name: Yondelis

Detailed Description:

The proposed investigation intends to explore if the combination of trabectedin and doxorubicin in the first line of treatment of advanced sarcomas obtains better results than doxorubicin monotherapy.

This proposal arises from the need to bring to the first line of treatment of advanced STS agents that have shown activity in second line. The goal is to improve available standard treatments. Tumors in patients not previously exposed to chemotherapy have not been selected in their biological behavior and they are the best scenario to test antitumor activity of a new anticancer drug.

The combination of drugs with different mechanisms of action may be a clear advantage to obtain better results and potential synergy. On the other hand, the toxicity profiles of both study drugs are different and worsening or summative of adverse effects is not expected.

The purpose of this study is to determine the efficacy of the combination of trabectedin and doxorubicin in comparison with doxorubicin alone in patients with advanced non operable and/or metastatic Soft Tissue Sarcomas (STS).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient must sign voluntarily the informed consent from before any study test is conducted that is not part of routine patient care, with the knowledge that he/she can abandon the study at any time without this affecting his/her previous care.
  • Aged between 18 and 70.
  • Pathological diagnosis of non operable and/or metastatic soft tissue sarcoma.
  • The following histological subtypes can be included:

    • Undifferentiated pleomorphic sarcoma (previously,malignant fibrous istiocytoma)
    • Leiomyosarcoma
    • Angiosarcoma
    • Liposarcoma
    • Synovial sarcoma
    • Fibrosarcoma
    • Hemangiopericytoma
    • Neurofibrosarcoma
    • Mixofibrosarcoma
    • Unclassified sarcoma
  • Measurable disease, according to RECIST criteria
  • Performance status 0-2 Eastern Cooperative Oncology Group(ECOG).
  • Adequate bone marrow function (hemoglobin > 10 g/dL, leukocytes ≥ 3.000/mm3, neutrophils ≥1.500/mm3, platelets ≥ 100.000/mm3). Patients with plasma creatinine ≤ 1,6 mg/dL, transaminases ≤2.5 times the upper limit of normal (ULN), total bilirubin ≤ upper limit of normal (ULN), CPK ≤ 2.5 times upper limit of normal (ULN), alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN) are acceptable. If the increase of alkaline phosphatase is > 2.5 times the upper limit of normal (ULN), then the alkaline phosphatase liver fraction and/or 5' nucleotidase and/or GGT must be ≤ upper limit of normal (ULN).
  • Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry.
  • Normal cardiac function with a Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or Multiple Uptake Gated Acquisition Scan (MUGA).

Exclusion Criteria:

  • Previous chemotherapy treatment.
  • Previous radiotherapy involving the only localization(s) of measurable tumoral disease.
  • Performance status> 2 Eastern Cooperative Oncology Group(ECOG).
  • Central Nervous System (CNS) metastases.
  • Plasma bilirubin > upper limit of normal(ULN).
  • Creatinine > 1.6 mg/dL.
  • History of other neoplastic disease with the exception of basalioma or in situ cervical cancer adequately treated.
  • Significant cardiovascular disease (for example, dyspnea > 2 NYHA)
  • Significant systemic diseases grade 3 or higher on the NCI-CTC version 3.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.
  • Uncontrolled bacterial, mycotic or viral infections.
  • Women who are pregnant or breast-feeding
  • Psychological, familial, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent.
  • Patients participating in another clinical trial or receiving any other investigational product.
  • Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion.
  • The following histologic subtypes are excluded:

    • Rhabdomyosarcoma
    • Ewing's family of tumors
    • Desmoplastic small round cell tumor
    • Clear cell sarcoma
    • Alveolar sarcoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104298

Locations
Spain
Ico Hospitalet
L'Hospitalet, Barcelona, Spain
ICO Badalona
Badalona, Spain
H. Clinic Barcelona
Barcelona, Spain
H. Sant Pau
Barcelona, Spain
H. Provincial Castellón
Castellón, Spain
ICO Girona
Girona, Spain
H. Xeral Cies
Lugo, Spain
Clinica Puerta Hierro
Madrid, Spain
H. Clínico. San Carlos
Madrid, Spain
H. U. La Paz
Madrid, Spain
H.U. Gregorio Marañon
Madrid, Spain
H.U. Ramon Y Cajal
Madrid, Spain
H.U. Clinico de Malaga
Málaga, Spain
H. de Navarra
Navarra, Spain
H. C. Asturias
Oviedo, Spain
H. Son Dureta
Palma de Mallorca, Spain
H. Univ. Canarias
Santa Cruz de Tenerife, Spain
H.U. Virgen Del Rocio
Sevilla, Spain
Instituto Valenciano de Oncología
Valencia, Spain
H. Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
Grupo Espanol de Investigacion en Sarcomas
Investigators
Principal Investigator: Javier Martin Broto, PhM GEIS
Principal Investigator: Andres Poveda, Ph.M. GEIS
  More Information

Responsible Party: Grupo Espanol de Investigacion en Sarcomas
ClinicalTrials.gov Identifier: NCT01104298     History of Changes
Other Study ID Numbers: GEIS-20  2008-008922-55 
Study First Received: April 13, 2010
Last Updated: October 26, 2015
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Keywords provided by Grupo Espanol de Investigacion en Sarcomas:
metastatic STS
Trabectedin
doxorrubicin
soft tissue sarcoma
non operable sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Trabectedin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 27, 2016