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

NCT ID: NCT01104298

Last Updated: 2015-10-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2014-05-31

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).

Conditions

Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Adriamycin; Yondelis

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Espanol de Investigacion en Sarcomas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Martin Broto, PhM

Role: PRINCIPAL_INVESTIGATOR

GEIS

Andres Poveda, Ph.M.

Role: PRINCIPAL_INVESTIGATOR

GEIS

Locations

Ico Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

ICO Badalona

Badalona, , Spain

H. Clinic Barcelona

Barcelona, , Spain

H. Sant Pau

Barcelona, , Spain

H. Provincial Castellón

Castellon, , 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

Seville, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

H. Miguel Servet

Zaragoza, , Spain

Countries

Spain

Other Identifiers

2008-008922-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEIS-20

Identifier Type: -

Identifier Source: org_study_id