A Study of ET-743 (Trabectedin) in Patients With Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the safety and effectiveness of an investigational chemotherapy agent in patients with advanced breast cancer.

Detailed Description
-----------------
Patients will be enrolled in the study after all study specific-entry criteria are met and informed consent is obtained. Patients will be required to attend regular clinic visits to receive study medication and have their status monitored. Patients will also be required to have radiologic tumor assessments performed at multiple times throughout the study. A detailed explanation can be provided by the study physician (Investigator) conducting this study. Trabectedin 580 mcg/m2 once weekly for 3 consecutive weeks (Treatment A) or 1,300 mcg/m2 once every 21 days (Treatment B) will be given to patients as a 3-hour intravenous (i.v). infusion via a central venous catheter which is a tube placed into a large vein that is used to administer medications. All patients will be given dexamethasone 10 mg i.v. 30 minutes before each trabectedin infusion. Patients may receive multiple cycles of trabectedin in the absence of disease progression.

Official Title
-----------------
A Phase 2 Study of ET-743 in Subjects With Advanced Breast Cancer

Conditions
-----------------
Breast Neoplasms, Neoplasms, Neoplasms by Site, Breast Diseases, Skin Diseases

Intervention / Treatment
-----------------
* Drug: ET743
* Drug: ET743


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of advanced breast cancer Prior therapy with anthracycline and taxane (2 types of chemotherapy drugs) At least one measureable tumor lesion Adequate bone marrow, hepatic and renal function Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Exclusion Criteria: Known hypersensitivity to any components of the i.v. formulation of ET-743 or dexamethasone Pregnant or lactating women Known metastases (spread) of cancer to the central nervous system History of another neoplastic disease unless in remission for five years or more.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>ET743 580 mcg/m2 3-hour i.v. infusion on Days 1 8 and 15 every 28 days for up to approximately 52 weeks in the absence of disease progression. Dexamethasone 10 mg i.v will be administered 30 minutes prior to each trabectedin infusion. | Drug: ET743<br>* 580 mcg/m2, 3-hour i.v. infusion, on Days 1, 8, and 15 every 28 days for up to approximately 52 weeks in the absence of disease progression. Dexamethasone, 10 mg i.v, will be administered 30 minutes prior to each trabectedin infusion.<br>|
| Experimental: 002<br>ET743 1 300 mcg/m2 3 hour i.v. infusion once every 21 days for up to approximately 52 weeks in the absence of disease progression. Dexamethasone 10 mg i.v will be administered 30 minutes prior to each trabectedin infusion. | Drug: ET743<br>* 1,300 mcg/m2, 3 hour i.v. infusion once every 21 days for up to approximately 52 weeks in the absence of disease progression. Dexamethasone, 10 mg i.v, will be administered 30 minutes prior to each trabectedin infusion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with objective response in each treatment arm. |  | Up to approximately 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | Up to approximately 52 weeks | 
| Time to progression (TTP) |  | Up to approximately 52 weeks | 
| Overall survival (OS) |  | Up to approximately 52 weeks | 
| The number of patients with treatment-emergent adverse events |  | Up to approximately 52 weeks | 
| Concentrations of trabectedin in plasma as a measure of the pharmacokinetics of trabectedin |  | During the first two 28-day treatment cycles | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Trabectedin, Yondelis, ET743, Advanced breast cancer, Breast, Cancer, Antineoplastic Agents, Alkylating Agents, Molecular Mechanisms of Pharmacological Action