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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Xian-Janssen Pharmaceutical Ltd.
Sponsor:
Information provided by (Responsible Party):
Xian-Janssen Pharmaceutical Ltd.
ClinicalTrials.gov Identifier:
NCT01692678
First received: August 6, 2012
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Advanced or Metastatic Liposarcoma or Leiomyosarcoma
Drug: Trabectedin
Drug: Dacarbazine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Open-label Study of YONDELIS (Trabectedin) in Subjects With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma

Resource links provided by NLM:


Further study details as provided by Xian-Janssen Pharmaceutical Ltd.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    MTD (1.5, 1.2 or 1.0 mg/m2) is determined by assessing Dose Limiting Toxicity (DLT).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    PFS is defined as the time from dosing to the occurrence of disease progression or death, whichever occurs first.

  • 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 ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization to the occurrence of disease progression or death, whichever occurs first.

  • 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 ] [ Designated as safety issue: No ]
    Time-to-progression (TTP) is defined as the time between dosing and disease progression.

  • 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 ] [ Designated as safety issue: No ]
    Time-to-progression (TTP) is defined as the time between randomization and disease progression.

  • 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 ] [ Designated as safety issue: No ]
    Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.

  • 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 ] [ Designated as safety issue: No ]
    Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Part 1: Observed maximum plasma concentration (Cmax) [ Time Frame: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmax of trabectedin will be determined

  • Part 1: Area under the plasma concentration-time curve (AUC) [ Time Frame: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter AUC of trabectedin will be determined.


Estimated Enrollment: 141
Study Start Date: August 2012
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.
Other Name: Dacarbazine

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01692678

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
China
Recruiting
Beijing, China
Suspended
Beijing, China
Suspended
Guangzhou, China
Suspended
Nanjing, China
Suspended
Shanghai, China
Active, not recruiting
Shanghai, China
Suspended
Tianjin, China
Sponsors and Collaborators
Xian-Janssen Pharmaceutical Ltd.
Investigators
Study Director: Xian-Janssen Pharmaceutical Ltd., China Clinical Trial Xian-Janssen Pharmaceutical Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Xian-Janssen Pharmaceutical Ltd.
ClinicalTrials.gov Identifier: NCT01692678     History of Changes
Other Study ID Numbers: CR017269, ET743SAR3006
Study First Received: August 6, 2012
Last Updated: July 15, 2014
Health Authority: China: Food and Drug Administration
China: Ethics Committee

Keywords provided by Xian-Janssen Pharmaceutical Ltd.:
Advanced or Metastatic liposarcoma or leiomyosarcoma
Sarcoma
L-sarcoma
Liposarcoma
Leiomyosarcoma
Trabectedin
Dacarbazine
Yondelis
Chinese patients
Overall survival
Pharmacokinetics

Additional relevant MeSH terms:
Leiomyosarcoma
Liposarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Adipose Tissue
Dacarbazine
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014