A Study of Trabectedin (YONDELIS) in Patients With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma

July 9, 2018 updated by: Xian-Janssen Pharmaceutical Ltd.

Multicenter, Open-label Study of YONDELIS (Trabectedin) in Subjects With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma

The purpose of this study is to find the optimal dose of trabectedin for Chinese patients with locally advanced or metastatic L-sarcoma (liposarcoma or leiomyosarcoma) who were previously treated (in any order) with at least an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen (Part 1) and to evaluate whether the overall survival (OS) of the trabectedin group is superior to dacarbazine group (Part 2).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study is divided into 2 separate parts (ie, Part 1 and Part 2). Part 1 is a dose finding part (to find the optimal dose) of trabectedin for Chinese patients, and Part 2 is a multicenter, randomized (the study medication is assigned by chance), active-controlled (an active substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), parallel-group (a study comparing the response in two or more groups of patients receiving different interventions), open-label (all people know the identity of the intervention) bridging part comparing the efficacy and safety of the optimal dose of trabectedin with dacarbazine in the same population as in Part 1. The study (in both Part 1 and Part 2) will consist of a screening phase, a treatment phase and a follow-up phase. Part 1: Optimal dose (ie, maximum tolerated dose [MTD]) is determined from the following 3 dose levels: Dose level 1 (1.5 mg/m2), Dose level 2 (1.2 mg/m2), and Dose level 3 (1.0 mg/m2)of trabectedin. Cohorts of 6 patients will be treated at each dose level. To determine MTD, dose limiting toxicity (DLT; any pre-defined adverse event that occurs during the first cycle ie, Cycle 1) will be determined. In the first cohort of 6 patients, (a) if DLT is less than or equal to 1 at a dose level, it is considered as MTD (b) if DLT is greater than 2, patients will be de-escalated to next dose level (c) if DLT is equal to 2, 3 more patients will be included at that dose level and if there will be no DLT in those 3 patients, that dose level is considered as MTD. Part 2: If the optimal dose found in Part 1 is 1.5 mg/m2, approximately 48 patients will be randomly assigned to either the trabectedin (approximately 32 patients) or dacarbazine (approximately 16 patients) treatment group in Part 2. If the optimal dose found in Part 1 is below 1.5 mg/m2, 123 patients will be randomly assigned to either the trabectedin (approximately 82 patients) or dacarbazine (approximately 41 patients) treatment group. Safety will be evaluated by assessing adverse events, clinical laboratory test, multiple gated acquisition scans, electrocardiograms, vital signs, and physical examination throughout the study up to 30 days after the end of treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
      • Shanghai, China

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically proven, unresectable, locally advanced or metastatic liposarcoma or leiomyosarcoma
  • Treated in any order with at least: an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen
  • Measurable disease at baseline in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Adequate recovery from prior therapy; all side effects (except alopecia) have resolved to Grade 1 or less according to the National Cancer Institute
  • Adequate organ function and hepatic function

Exclusion Criteria:

  • Prior exposure to trabectedin (both Part 1 and Part 2) or dacarbazine (Only Part 2)
  • Less than 3 weeks from last dose of systemic cytotoxic therapy, radiation therapy, or therapy with any investigational agent
  • Other malignancy within past 3 years (exceptions: basal or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage 1 carcinoma of the cervix)
  • Known central nervous system metastasis
  • Active or symptomatic viral hepatitis or chronic liver disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Trabectedin (Part 1 and Part 2)
Trabectedin will be administered at a dose of 1.5, 1.2 or 1.0 mg/m2 as a 24-hour intravenous infusion on Day 1 of each 21-day treatment cycle (ie, each treatment cycle being at least 21 days apart).
Drug: Trabectedin
Type=exact number, unit=mg/m2, number=1.5, 1.2 or 1.0, form=solution, route=intravenous infusion. Trabectedin will be administered on Day 1 of each 21-day treatment cycle.
Other Names:
  • YONDELIS
ACTIVE_COMPARATOR: Dacarbazine (Part 2)
Dacarbazine will be administered at a dose of 1 g/m2 as a longer than 30-minute intravenous infusion on Day 1 of each 21-day treatment cycle (ie, each treatment cycle being at least 21 days apart).
Drug: Dacarbazine
Type=exact number, unit=g/m2, number=1, form=solution, route=intravenous infusion. Dacarbazine will be administered on Day 1 of each 21-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Optimal dose level (Maximum tolerated dose [MTD]) of trabectidin
Time Frame: From the date of dosing until 21days after the date of last patient enrolled
MTD (1.5, 1.2 or 1.0 mg/m2) is determined by assessing Dose Limiting Toxicity (DLT).
From the date of dosing until 21days after the date of last patient enrolled
Part 1: Overall survival
Time Frame: From the date of dosing upto 18 months after the last patient enrollment or 30 days after the last dose of study medication has been administered, whichever will be later
Patients will be monitored for survival status at least every 60 days for the first 2 years after the last dose of study drug and every 90 days thereafter.
From the date of dosing upto 18 months after the last patient enrollment or 30 days after the last dose of study medication has been administered, whichever will be later
Part 2: Overall survival
Time Frame: From the date of randomization until the required number of events has occurred (approximately 32 if 1.5mg/m2, or 82 with below 1.5mg/m2) as assessed approximately for 6 months after the last patient enrollment
Patients will be monitored for survival status at least every 60 days for the first 2 years after the last dose of study drug and every 90 days thereafter.
From the date of randomization until the required number of events has occurred (approximately 32 if 1.5mg/m2, or 82 with below 1.5mg/m2) as assessed approximately for 6 months after the last patient enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1: Progression free survival (PFS)
Time Frame: From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed up to 18 months after the last patient enrollment
PFS is defined as the time from dosing to the occurrence of disease progression or death, whichever occurs first.
From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed up to 18 months after the last patient enrollment
Part 2: Progression free survival (PFS)
Time Frame: From the date of randomization till the first documented disease progression or death whichever comes first until the required number of events, estimate of 6 months after the last patient enrollment
PFS is defined as the time from randomization to the occurrence of disease progression or death, whichever occurs first.
From the date of randomization till the first documented disease progression or death whichever comes first until the required number of events, estimate of 6 months after the last patient enrollment
Part 1: Time-to-progression (TTP)
Time Frame: From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed up to 18 months after the last patient enrollment
Time-to-progression (TTP) is defined as the time between dosing and disease progression.
From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed up to 18 months after the last patient enrollment
Part 2: Time-to-progression (TTP)
Time Frame: From the date of randomization till the first documented disease progression or death whichever comes first until the required number of events, estimate of 6 months after the last patient enrollment
Time-to-progression (TTP) is defined as the time between randomization and disease progression.
From the date of randomization till the first documented disease progression or death whichever comes first until the required number of events, estimate of 6 months after the last patient enrollment
Part 1: Objective Response Rate (ORR)
Time Frame: From date of dosing until the date of best response, as assessed up to 18 months after the last patient enrollment
Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.
From date of dosing until the date of best response, as assessed up to 18 months after the last patient enrollment
Part 2: Objective Response Rate (ORR)
Time Frame: From date of dosing until the date of best response, as assessed up to 6 months after the last patient enrollment
Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.
From date of dosing until the date of best response, as assessed up to 6 months after the last patient enrollment
Part 1: Duration of response (DR)
Time Frame: From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed approximately up to 18 months after the last patient enrollment
Duration of response (DR) is defined only for patients who have CR or PR as best overall response and is calculated from the date of the first documentation of response to the date of disease progression or death, whichever occurs first.
From date of dosing until the date of first documented progression or date of death from any cause, whichever comes first, as assessed approximately up to 18 months after the last patient enrollment
Part 2: Duration of response (DR)
Time Frame: From the date of randomization till the first documented disease progression or death whichever comes first, assessed approximately up to 6 months after the last patient enrollment
Duration of response (DR) is defined only for patients who have CR or PR as best overall response and is calculated from the date of the first documentation of response to the date of disease progression or death, whichever occurs first.
From the date of randomization till the first documented disease progression or death whichever comes first, assessed approximately up to 6 months after the last patient enrollment
Part 1: Observed maximum plasma concentration (Cmax)
Time Frame: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles
Pharmacokinetic parameter Cmax of trabectedin will be determined
Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles
Part 1: Area under the plasma concentration-time curve (AUC)
Time Frame: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles
Pharmacokinetic parameter AUC of trabectedin will be determined.
Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xian-Janssen Pharmaceutical Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 7, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 11, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 11, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 6, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR017269
  • ET743SAR3006 (OTHER: Xian-Janssen Pharmaceutical Ltd., China)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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