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
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
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
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).
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:
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:
Navarra, Spain