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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

16

Phase

  • 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

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
Intervention / Treatment
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

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

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

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)

August 7, 2012

Primary Completion (ACTUAL)

October 11, 2016

Study Completion (ACTUAL)

October 11, 2016

Study Registration Dates

First Submitted

August 6, 2012

First Submitted That Met QC Criteria

September 20, 2012

First Posted (ESTIMATE)

September 25, 2012

Study Record Updates

Last Update Posted (ACTUAL)

July 11, 2018

Last Update Submitted That Met QC Criteria

July 9, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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