Clinical Trial Of Doxorubicin Versus Trabectedin Plus Doxorubicin In The First Line Treatment Of Patients With Advanced Non Operable And/Or Metastatic Soft Tissue Sarcomas

Overview[ - collapse ][ - ]

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. 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).
ConditionSarcoma
InterventionDrug: Doxorubicin
Drug: Trabectedin plus Doxorubicin
PhasePhase 2
SponsorGrupo Espanol de Investigacion en Sarcomas
Responsible PartyGrupo Espanol de Investigacion en Sarcomas
ClinicalTrials.gov IdentifierNCT01104298
First ReceivedApril 13, 2010
Last UpdatedApril 27, 2010
Last verifiedApril 2010

Tracking Information[ + expand ][ + ]

First Received DateApril 13, 2010
Last Updated DateApril 27, 2010
Start DateNovember 2009
Estimated Primary Completion DateNot Provided
Current Primary Outcome MeasuresTo 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.
Current 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.

Descriptive Information[ + expand ][ + ]

Brief TitleClinical Trial Of Doxorubicin Versus Trabectedin Plus Doxorubicin In The First Line Treatment Of Patients With Advanced Non Operable And/Or Metastatic Soft Tissue Sarcomas
Official TitleRandomized, 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
Brief Summary
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).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionSarcoma
InterventionDrug: 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.
Drug: Trabectedin plus Doxorubicin
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.
Study Arm (s)
  • 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
  • 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment182
Estimated Completion DateNot Provided
Estimated Primary Completion DateDecember 2012
Eligibility 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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Javier Martin, PhM
+34934344412
secretaria@grupogeis.org
Location CountriesSpain

Administrative Information[ + expand ][ + ]

NCT Number NCT01104298
Other Study ID NumbersGEIS-20
Has Data Monitoring CommitteeYes
Information Provided ByGrupo Espanol de Investigacion en Sarcomas
Study SponsorGrupo Espanol de Investigacion en Sarcomas
CollaboratorsNot Provided
Investigators Principal Investigator: Javier Martin Broto, PhM GEISPrincipal Investigator: Andres Poveda, Ph.M. GEIS
Verification DateApril 2010

Locations[ + expand ][ + ]

Ico Hospitalet
L'Hospitalet, Barcelona, Spain
Principal Investigator: Xavier García del Muro, Ph.M.
Recruiting
ICO Badalona
Badalona, Spain
Principal Investigator: Carmen Balañá, Ph.M.
Recruiting
H. Clinic Barcelona
Barcelona, Spain
Principal Investigator: Joan Maurel Santasusana, Phm
Recruiting
H. Sant Pau
Barcelona, Spain
Principal Investigator: Antonio López Pousa, Ph.M.
Recruiting
H. Provincial Castellón
Castellón, Spain
Principal Investigator: Ramón De las Peñas, Ph.M
Recruiting
ICO Girona
Girona, Spain
Principal Investigator: Jordi Rubió, Ph.M.
Recruiting
H. Xeral Cies
Lugo, Spain
Principal Investigator: Juan A Carrasco, Ph.M.
Recruiting
H. Clínico. San Carlos
Madrid, Spain
Principal Investigator: Antonio Casado, Ph.M.
Recruiting
Clinica Puerta Hierro
Madrid, Spain
Principal Investigator: Ricardo Cubedo, Ph.M.
Recruiting
H.U. Gregorio Marañon
Madrid, Spain
Principal Investigator: Rosa Álvarez, Ph.M.
Recruiting
H. U. La Paz
Madrid, Spain
Principal Investigator: Andres Redondo, Ph. M
Recruiting
H.U. Ramon Y Cajal
Madrid, Spain
Principal Investigator: María Ángeles Vaz, Ph.M.
Recruiting
H.U. Clinico de Malaga
Málaga, Spain
Principal Investigator: Isabel Sevilla, Ph.M.
Recruiting
H. de Navarra
Navarra, Spain
Principal Investigator: Nuria Laínez, Ph.M.
Recruiting
H. C. Asturias
Oviedo, Spain
Principal Investigator: Joaquin Fra, Ph.M.
Recruiting
H. Son Dureta
Palma de Mallorca, Spain
Principal Investigator: Javier Martín Broto, Ph.M.
Recruiting
H. Univ. Canarias
Santa Cruz de Tenerife, Spain
Principal Investigator: Josefina Cruz, Ph.M.
Recruiting
H.U. Virgen Del Rocio
Sevilla, Spain
Principal Investigator: Flor Oncala, Ph.M.
Recruiting
Instituto Valenciano de Oncología
Valencia, Spain
Principal Investigator: Andres Poveda, Ph.M.
Recruiting
H. Miguel Servet
Zaragoza, Spain
Principal Investigator: Javier Martínez Trufero, Ph.M.
Recruiting