A Study to Assess Treatment With 2 Different Dosing Schedules of Trabectidin Administered to Patients With Advanced Cancer

Study Overview
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Brief Summary
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The purpose of this study is to test the safety and effectiveness of an investigational chemotherapy agent in patients with types of advanced cancer referred to as liposarcoma or leiomyosarcoma.

Detailed Description
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This is an open-label (patients will know the names of the study drugs they receive), randomized (patients will be assigned by chance to receive 1 of 2 treatment schedules with trabectidin) study designed to examine the the survival, safety, and pharmacokinetics (blood levels) trabectedin when administered to patients with 2 types of cancer (Liposarcoma or Leiomyosarcoma) who have received treatment with other anti-cancer therapy (Anthracycline and/or Ifosfamide). Trabectedin (also referred to as Yondelis) is a drug being developed to treat patients with cancer. Yondelis will be administered intravenously (i.v.) via a central catheter (tube) into a central vein once a week (0.58 mg/m2 as a 3-hour infusion on Days 1, 8, and 15 of each 28-day treatment cycle) or once every 3 weeks (1.5 mg/m2 administered as a 24-hour infusion on Day 1 of every 21-day treatment cycle) until disease progression. Patients in each arm will be pretreated with 20 mg of dexamethasone i.v. 30 minutes prior to each infusion.

Official Title
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A Randomized, Multicenter, Open-label Study of Yondelis (ET-743 Ecteinascidin) Administered by 2 Different Schedules (Weekly for 3 of 4 Weeks vs. q3 Weeks) in Subjects With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma Following Treatment With an Anthracycline and Ifosfamide

Conditions
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Liposarcoma, Leiomyosarcoma

Intervention / Treatment
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* Drug: Yondelis
* Drug: Yondelis
* Drug: Dexamethasone
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have advanced liposarcoma or leiomyosarcoma that has metastasized (spread) Have a pathology specimen available for centralized review Have progressive or relapsed (reappearance of) disease, received treatment with anthracycline and/or ifosfamide before enrollment in study, and have at least one measurable tumor lesion Have adequate bone marrow, liver and kidney function Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: Previous exposure to Yondelis i.v. formulation, ET-743 (ecteinascidin) Cancer that has metastasized (spread) to the central nervous system Active viral hepatitis or chronic liver disease Unstable cardiac (heart) condition including congestive heart failure or angina pectoris (heart pain), myocardial infarction (heart attack) within 1 year before enrollment History of another neoplastic (malignant or nonmalignant tumor) disease (except basal cell carcinoma or cervical carcinoma adequately treated), unless in remission for 5 years or more before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yondelis weekly schedule<br>Yondelis weekly schedule: 0.58 mg/m2 administered as a 3-hour i.v. infusion on Days 1 8 and 15 of each 28-day treatment cycle. Patients will be pretreated with 10 mg of dexamethasone i.v. 30 minutes prior to each infusion. | Drug: Yondelis<br>* 0.58 mg/m2 administered as a 3-hour i.v. infusion on Days 1, 8, and 15 of each 28-day treatment cycle.<br>Drug: Dexamethasone<br>* Pretreatment with 10 mg of dexamethasone i.v. 30 minutes prior to each Yondelis infusion on Days 1, 8, and 15 of each 28-day treatment cycle.<br>|
| Experimental: Yondelis once every 3 weeks schedule<br>Yondelis once every 3 weeks schedule: 1.5 mg/m2 administered as a 24-hour i.v. infusion on Day 1 of every 21-day treatment cycle. Patients will be pretreated with 20 mg of dexamethasone i.v. on Day 1 of each treatment cycle 30 minutes prior to each infusion. | Drug: Yondelis<br>* 1.5 mg/m2 administered as a 24-hour i.v. infusion on Day 1 of every 21-day treatment cycle.<br>Drug: Dexamethasone<br>* Pretreatment with 20 mg of dexamethasone i.v. on Day 1 of each 21- day treatment cycle, 30 minutes prior to each Yondelis infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression- Independent Review | Time to Progression was defined as time between randomization and the first documentation of disease progression or death due to progressive disease. | From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Objective Response - Independent Review | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. | From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years | 
| Duration of Response - Independent Review | Duration of response based on assessment of confirmed CR or confirmed PR according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. Kaplan-Meier estimation of response duration was used to account censored participants with ongoing response. | From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years | 
| Progression-Free Survival - Independent Review | The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression. | From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years | 
| Overall Survival | The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression. | From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trabectedin, Yondelis, ET-743, Ecteinascidin, Anthracycline, Ifosfamide, Dexamethasone, Intravenous, Cancer, Malignant, Metastatic