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

Purpose

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	Intervention	Phase
Liposarcoma Leiomyosarcoma	Drug: Yondelis Drug: Dexamethasone	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Drug Information available for: Dexamethasone Dexamethasone sodium phosphate Ifosfamide Dexamethasone acetate Trabectedin

Genetic and Rare Diseases Information Center resources: Liposarcoma Leiomyosarcoma Malignant Mesenchymal Tumor Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression.
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 ] [ Designated as safety issue: No ]
The below table shows Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression.


Enrollment:	271
Study Start Date:	May 2003
Study Completion Date:	May 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060944

Show 41 Study Locations

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. This link exits the ClinicalTrials.gov site


Responsible Party:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00060944 History of Changes
Other Study ID Numbers:	CR004336 ET743-STS-201
Study First Received:	May 16, 2003
Results First Received:	January 14, 2014
Last Updated:	August 28, 2014
Health Authority:	United States: Food and Drug Administration

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 acetate Dexamethasone Dexamethasone 21-phosphate Trabectedin Ifosfamide 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

ClinicalTrials.gov processed this record on September 23, 2016