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

• ClinicalTrials.gov Identifier: NCT00060944
• Recruitment Status: Completed
• First Posted: May 19, 2003
• Results First Posted: September 8, 2014
• Last Update Posted: September 8, 2014
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborator: PharmaMar
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Liposarcoma; Leiomyosarcoma	Drug: Yondelis; Drug: Dexamethasone	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 2003
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Yondelis weekly schedule; 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; 0.58 mg/m2 administered as a 3-hour i.v. infusion on Days 1, 8, and 15 of each 28-day treatment cycle.; Drug: Dexamethasone; 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.
Experimental: Yondelis once every 3 weeks schedule; 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; 1.5 mg/m2 administered as a 24-hour i.v. infusion on Day 1 of every 21-day treatment cycle.; Drug: Dexamethasone; Pretreatment with 20 mg of dexamethasone i.v. on Day 1 of each 21- day treatment cycle, 30 minutes prior to each Yondelis infusion.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Percentage of Participants Objective Response - Independent Review [ Time Frame: From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years ]
   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.
2. Duration of Response - Independent Review [ Time Frame: 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 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.
3. Progression-Free Survival - Independent Review [ Time Frame: From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years ]
   The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression.
4. Overall Survival [ Time Frame: From randomization to the first documentation of disease progression or death due to progressive disease, whichever occurs first, assessed up to 5 years ]
   The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Los Angeles, California, United States

United States, Colorado

Aurora, Colorado, United States

United States, Idaho

Coeur D Alene, Idaho, United States

United States, Illinois

Park Ridge, Illinois, United States

United States, Indiana

Indianapolis, Indiana, United States

United States, Kentucky

Louisville, Kentucky, United States

United States, Massachusetts

Boston, Massachusetts, United States

United States, Michigan

Ann Arbor, Michigan, United States

United States, Minnesota

Minneapolis, Minnesota, United States

Rochester, Minnesota, United States

United States, New Jersey

Newark, New Jersey, United States

United States, New York

New York, New York, United States

United States, Ohio

Cleveland, Ohio, United States

United States, Oregon

Portland, Oregon, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, Tennessee

Nashville, Tennessee, United States

United States, Texas

Houston, Texas, United States

United States, Utah

Salt Lake City, Utah, United States

United States, Washington

Seattle, Washington, United States

United States, Wisconsin

Milwaukee, Wisconsin, United States

Australia

East Melbourne, Australia

Newcastle, Australia

Perth, Australia

Woodville, Australia

Belgium

Leuven, Belgium

Canada, Alberta

Calgary, Alberta, Canada

Canada, Ontario

London, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Canada

Edmonton, Canada

France

Lyon, France

Villejuif, France

Germany

Düsseldorf, Germany

Russian Federation

Moscow N/A, Russian Federation

Moscow, Russian Federation

Obninsk N/A, Russian Federation

Samara N/A, Russian Federation

St Petersburg N/A, Russian Federation

St Petersburg, Russian Federation

Spain

Barcelona, Spain

Valencia N/A, Spain

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

PharmaMar

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More Information

Additional Information:

Demetri GD et al. J Clin Oncol. 2009;27(25):4188-96. 

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00060944
• Other Study ID Numbers: CR004336; ET743-STS-201 ( Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C. )
• First Posted: May 19, 2003
• Results First Posted: September 8, 2014
• Last Update Posted: September 8, 2014
• Last Verified: August 2014

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Trabectedin; Yondelis; ET-743; Ecteinascidin; Anthracycline; Ifosfamide; Dexamethasone; Intravenous; Cancer; Malignant; Metastatic

Additional relevant MeSH terms:

Leiomyosarcoma; Liposarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue; Dexamethasone; Dexamethasone acetate; Ifosfamide; Trabectedin; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents