Clinical trial NCT01104298: Doxorubicin vs. Trabectedin Plus Doxorubicin in Non Operable and/or Metastatic STS
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sarcoma
Keywords: metastatic STS
Trabectedin
doxorrubicin
soft tissue sarcoma
non operable sarcoma
Lead sponsor: Grupo Espanol de Investigacion en Sarcomas
Sponsor class: OTHER
First posted: 2010-04-15
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: 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)
timeFrame: 2012
Secondary outcomes:
measure: To determine activity by means of RECIST objective responses in both study arms, trabectedin/doxorubicin combination and the control arm.
timeFrame: 2012
measure: To determine the tumor control (response rates plus stabilizations) in both arms of treatment.
timeFrame: 2012
measure: Overall survival.
timeFrame: 2012
measure: To determine activity by tissue changes applying the Choi criteria to Soft Tissue Sarcomas (STS)(see radiological review sub study).
timeFrame: 2012
measure: To determine toxicity of trabectedin/doxorubicin combination and the control arm.
timeFrame: 2012
measure: 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.
timeFrame: 2012
measure: 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.
timeFrame: 2012
Other outcomes:
Locations:
city: L'Hospitalet
country: Spain
facility: Ico Hospitalet
state: Barcelona
city: Badalona
country: Spain
facility: ICO Badalona
city: Barcelona
country: Spain
facility: H. Clinic Barcelona
city: Barcelona
country: Spain
facility: H. Sant Pau
city: Castellón
country: Spain
facility: H. Provincial Castellón
city: Girona
country: Spain
facility: ICO Girona
city: Lugo
country: Spain
facility: H. Xeral Cies
city: Madrid
country: Spain
facility: Clinica Puerta Hierro
city: Madrid
country: Spain
facility: H. Clínico. San Carlos
city: Madrid
country: Spain
facility: H. U. La Paz
city: Madrid
country: Spain
facility: H.U. Gregorio Marañon
city: Madrid
country: Spain
facility: H.U. Ramon Y Cajal
city: Málaga
country: Spain
facility: H.U. Clinico de Malaga
city: Navarra
country: Spain
facility: H. de Navarra
city: Oviedo
country: Spain
facility: H. C. Asturias
city: Palma de Mallorca
country: Spain
facility: H. Son Dureta
city: Santa Cruz de Tenerife
country: Spain
facility: H. Univ. Canarias
city: Sevilla
country: Spain
facility: H.U. Virgen Del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Zaragoza
country: Spain
facility: H. Miguel Servet
Study officials:
affiliation: GEIS
name: Javier Martin Broto, PhM
role: PRINCIPAL_INVESTIGATOR
affiliation: GEIS
name: Andres Poveda, Ph.M.
role: PRINCIPAL_INVESTIGATOR
References: