Advanced or Metastatic Liposarcoma or LeiomyosarcomaPhase 3NCT01692678
A Study of Trabectedin (YONDELIS) in Patients With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma
A Phase 3 study testing Trabectedin and Dacarbazine in people with Advanced or Metastatic Liposarcoma or Leiomyosarcoma, run by Xian-Janssen Pharmaceutical Ltd. at 2 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Advanced or Metastatic Liposarcoma or Leiomyosarcoma
- What is being tested?
- Trabectedin and Dacarbazine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesChina
- Study dates
- 7 Aug 2012to 11 Oct 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: 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).
Read the 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.
- Being tested
- Trabectedin, Dacarbazine
- Keywords
- Advanced or Metastatic liposarcoma or leiomyosarcoma, Sarcoma, L-sarcoma, Liposarcoma, Leiomyosarcoma, Trabectedin, Dacarbazine, Yondelis, Chinese patients, Overall survival, Pharmacokinetics
- Medical subject headings
- Liposarcoma, Leiomyosarcoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrabectedinDrug
Also called YONDELIS
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.
DacarbazineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Trabectedin (Part 1 and Part 2) | Experimental | 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). Receives: Drug: Trabectedin |
| Dacarbazine (Part 2) | Active comparator | 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). Receives: Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Optimal dose level (Maximum tolerated dose [MTD]) of trabectidin
MTD (1.5, 1.2 or 1.0 mg/m2) is determined by assessing Dose Limiting Toxicity (DLT).
Measured: From the date of dosing until 21days after the date of last patient enrolled
Part 1: Overall survival
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.
Measured: 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
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.
Measured: 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 outcomes (10)
Part 1: Progression free survival (PFS)
PFS is defined as the time from dosing to the occurrence of disease progression or death, whichever occurs first.
Measured: 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)
PFS is defined as the time from randomization to the occurrence of disease progression or death, whichever occurs first.
Measured: 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-to-progression (TTP) is defined as the time between dosing and disease progression.
Measured: 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-to-progression (TTP) is defined as the time between randomization and disease progression.
Measured: 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)
Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.
Measured: 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)
Objective Response Rate (ORR) is defined as having complete response or partial response as best overall response based on reconciled radiographic disease assessment.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Pharmacokinetic parameter Cmax of trabectedin will be determined
Measured: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles
Part 1: Area under the plasma concentration-time curve (AUC)
Pharmacokinetic parameter AUC of trabectedin will be determined.
Measured: Days 1, 2, 3, 4, 5, 8 of first 2 treatment cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study start7 Aug 2012
- Primary completion11 Oct 2016
- Study completion11 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Liposarcoma or LeiomyosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xian-Janssen Pharmaceutical Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xian-Janssen Pharmaceutical Ltd., China Clinical Trial, Study director, Xian-Janssen Pharmaceutical Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01692678
- Sponsor's protocol ID
- CR017269
- Other IDs
- ET743SAR3006
- Status last verified
- Jul 2018
- First submitted
- 6 Aug 2012
- Last updated
- 11 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Open-label Study of YONDELIS (Trabectedin) in Subjects With Locally Advanced or Metastatic Liposarcoma or Leiomyosarcoma
- ClinicalTrials.gov ID
- NCT01692678
- Acronym / sponsor ID
- CR017269
- Keywords
- Advanced or Metastatic liposarcoma or leiomyosarcoma, Sarcoma, L-sarcoma, Liposarcoma, Leiomyosarcoma, Trabectedin, Dacarbazine, Yondelis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Xian-Janssen Pharmaceutical Ltd.Industry (pharma, biotech, devices)
- Study start
- 7 Aug 2012 (actual)
- Primary completion
- 11 Oct 2016 (actual)
- Study completion
- 11 Oct 2016 (actual)
- First posted
- 25 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trabectedin (Part 1 and Part 2) | Experimental | Drug: TrabectedinTrabectedin 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). |
| Dacarbazine (Part 2) | Active comparator | Drug: DacarbazineDacarbazine 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). |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrabectedinAlso: YONDELISType=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. | Drug | Trabectedin (Part 1 and Part 2) |
| DacarbazineType=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. | Drug | Dacarbazine (Part 2) |
Primary outcome
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).
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.
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.
10 secondary outcomes
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
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
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
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
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
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
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
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
Part 1: Observed maximum plasma concentration (Cmax)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2018.
- Multicenter, Open-label Study of YONDELIS (Trabectedin) in Subjects With Locally Advanced or Metastatic Liposarcoma or LeiomyosarcomaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xian-Janssen Pharmaceutical Ltd., China Clinical Trial study director
Xian-Janssen Pharmaceutical Ltd.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trabectedin and Dacarbazine in people with Advanced or Metastatic Liposarcoma or Leiomyosarcoma, run by Xian-Janssen Pharmaceutical Ltd. at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2018.