Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication YONDELIS ® is indicated for the treatment of adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen [see Clinical Studies (14) ] . YONDELIS is an alkylating drug indicated for the treatment of adult patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen ( 1 ) FDA label
Also known as Yondelis, ET-743
Trabectedin · 14 trials · 26 indications
OS is defined as the time between the date of randomization and the date of death. Participants who died, regardless of the cause of death, were considered to have had an event.
The PFS was assessed as median number of days from the date of randomization until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
PFS is defined as the time between randomization and disease progression or death.
QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Fridericia correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.
QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Bazett's Correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Percentage of participants with confirmed objective response will be based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR is defined as disappearance of all target lesions. PR is those with at least 30 percent decrease in the sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. IER will be done to re-examine all Investigator assessed outcomes.
Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. The CR is defined as disappearance of all target lesions. The PR is those with at least 30 percent decrease in the sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions.
Complete pathological response is complete disappearance of the tumor tissue up to the molecular level.
The PSA response will be evaluated according to National Cancer Institute PSA Working Group criterion, which is, greater than or equal to 50 percent decrease in PSA from Baseline after the first dose of study drug, which would be subsequently confirmed by a measurement, that is, at least 4 or more weeks after initial documentation of PSA.
Time to Progression was defined as time between randomization and the first documentation of disease progression or death due to progressive disease.
This will be measured when ketoconazole will be administered.
| Arm | Type | Description |
|---|---|---|
| Arm A: trabectedin + DOXIL | EXPERIMENTAL | Participants will receive DOXIL 30 millgram per meter square (mg/m\^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m\^2 administered as an IV infusion over approximately 3hours, every 3 weeks. Participants will be pretreated with 20 mg dexamethasone IV (or the IV equivalent) approximately 30 minutes before DOXIL study drug. As of Amendment 6, treatment with trabectedin will be discontinued for participants on treatment with trabectedin and no new participants will receive trabectedin. Participants who, in the opinion of the investigator, are deriving clinical benefit may continue treatment with single-agent DOXIL as per the local standard of care. |
| Arm B: DOXIL | ACTIVE_COMPARATOR | Participants will receive DOXIL, 50 mg/m\^2 administered as an IV infusion over approximately 90 minutes every 4 weeks. |
| Trabectedin | EXPERIMENTAL | - |
| Dacarbazine | ACTIVE_COMPARATOR | - |
| Doxorubicin plus Ifosfamide | ACTIVE_COMPARATOR | Doxorubicin (as a monotherapy) 75 mg per m\^2 will be given intravenously every 3 weeks or Doxorubicin 60 mg per m\^2 will be given intravenously every 3 weeks followed by ifosfamide 6 to 9 gram (g)/m\^2 every 3 weeks until disease progression. |
| DOXIL + trabectedin | EXPERIMENTAL | Combination arm - Trabectedin + DOXIL: DOXIL 30 mg/m2 intravenous (IV) infusion over 90 minutes + trabectedin 1.1 mg/m2 IV infusion over 3 hours every 3 weeks. patients will be premedicated with 20 mg dexamethasone or its equivalent IV infusion over 30 minutes prior to the DOXIL infusion. |
| DOXIL | ACTIVE_COMPARATOR | Monotherapy arm - DOXIL: 50 mg/m2 IV infusion over 90 minutes every 4 weeks. |
| Group A | EXPERIMENTAL | Participants with triple negative phenotype: estrogen receptor, progesterone receptor and human estrogen receptor-2 (HER-2) negative status for breast cancer (abnormal tissue that grows and spreads in the body until it kills) will receive trabectedin 1.3 milligram per meter square (mg/m\^2) intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over 3-hours (hrs) every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72hrs after the start of study drug infusion from Day 1 to 3. |
| Group B | EXPERIMENTAL | Participants with overexpressing HER-2 breast cancer will receive trabectedin 1.3 mg/m\^2 intravenous infusion over 3-hrs every 3 weeks, on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 milligram (mg) orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3. |
| Group C | EXPERIMENTAL | Participants with familial breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2) mutation carriers cancer will receive trabectedin 1.3 mg/m\^2 intravenous infusion over 3-hrs every 3 weeks on Day 1 of each cycle. Each cycle length will be 3 weeks. Treatment will be continued until disease progression, unmanageable toxicity, participant refusal or treatment delay no longer than 3 weeks due to toxicity. Along with study drug participants will be given dexamethasone 4 mg orally 24 hrs and 12hrs before study drug infusion on Day -1, followed by dexamethasone 20 mg intravenously 30 minutes before study drug infusion on Day 1, followed by dexamethasone 4 mg orally 24, 36, 48, 60 and 72 hrs after the start of study drug infusion from Day 1 to 3. |
| Trabectedin 0.58 milligram per square meter (mg/m^2) | EXPERIMENTAL | Trabectedin will be administered as 3-hour intravenous infusion at dose of 0.58 mg/m\^2 weekly on Day 1, 8 and 15 in 28-day cycle and will be continued until disease progression or unacceptable toxicity. |
| Trabectedin 1.5 mg/m^2 | EXPERIMENTAL | Trabectedin will be administered at dose of 1.5 mg/m\^2 as 24-hour infusion every three weeks, and will be continued until disease progression or unacceptable toxicity. |
| Trabectedin 1.2 mg/m^2 | EXPERIMENTAL | Trabectedin will be administered at dose of 1.2 mg/m\^2 as 24-hour infusion every three weeks, and will be continued until disease progression or unacceptable toxicity. |
| Yondelis weekly schedule | EXPERIMENTAL | 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. |
| Yondelis once every 3 weeks schedule | EXPERIMENTAL | 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. |
| Part 1 | EXPERIMENTAL | Patients will receive trabectedin+ketoconazole followed by trabectedin alone. Each cycle will be will be separated by 21 days. Patients will receive 6 total consecutive doses of ketoconazole. Dexamethasone or equivalent steroid will be administered before trabectedin in each cycle. |
| Part 2 | EXPERIMENTAL | Patients will receive 1 of 2 treatment sequences; Sequence 1: trabectedin+ketoconazole followed by trabectedin alone or Sequence 2: trabectedin alone followed by trabectedin+ketoconazole. Each cycle will be separated by 21 days. Patients will receive 15 total consecutive doses of ketoconazole. Dexamethasone or equivalent steroid will be administered before trabectedin in each cycle. |
| Trabectedin 1.3 mg/m^2 plus Dexamethasone | EXPERIMENTAL | Control group Trabectedin 1.3 mg/m\^2 i.v.will be administered on Day 1. Dexamethasone will be administered 30 minutes prior to trabectedin. |
| Trabectedin 0.58 mg/m^2 plus Dexamethasone | EXPERIMENTAL | Hepatic dysfunction group Trabectedin 0.58 mg/m\^2 (or adjusted dose) i.v. will be administered on Day 1. Dexamethasone will be administered 30 minutes prior to trabectedin. |
| Trabectedin and doxorubicin | EXPERIMENTAL | Doxorubicin (50 to 75 mg/m2) administered intravenously on Day 1 followed by trabectedin (0.9 to 1.3 mg/m2) administered intravenously on Day 1 every 3 weeks for up to 6 cycles. Dexamethasone 20 mg administered intravenously will be given within 1 hour before the start of doxorubicin. Patients may receive filgrastim for unmanageable neutropenia. |
| Name | Type | Description |
|---|---|---|
| Trabectedin | DRUG | 1.1 mg/m\^2 administered intravenously over approximately 3 hours on Day 1 of each 21-day treatment cycle. |
| DOXIL | DRUG | 30 mg/m\^2 administered intravenously over approximately 90 minutes on Day 1 of each 21-day treatment cycle. |
| Dexamethasone | DRUG | 20 mg administered intravenously on Day 1 of each 21-day treatment cycle approximately 30 minutes prior to study drug infusion. |
| Dacarbazine | DRUG | Type=exactly number, unit=g/m2, number=1, form=intravenous infusion, route=intravenous use. Once every 3 weeks until disease progression or signs of toxicity. |
| Doxorubicin | DRUG | Doxorubicin 60 or 75 mg/m\^2 will be given intravenously every 3 weeks until disease progression. |
| Ifosfamide | DRUG | Ifosfamide 6 to 9 g/m\^2 will be given intravenously every 3 weeks until disease progression. |
| Placebo | DRUG | Participants will receive 3-hour placebo intravenous infusion on Day 1. |
| Yondelis | DRUG | 1.5 mg/m2 administered as a 24-hour i.v. infusion on Day 1 of every 21-day treatment cycle. |
| Ketoconazole | DRUG | Patients will receive ketoconazole 1 X 200 mg tablet, two times a day, orally (by mouth) |
| Dexamethasone or equivalent steroid | DRUG | Patients will receive dexamethasone 20 mg or equivalent steroid intravenously, 30 minutes before trabectedin in each cycle. |
Inclusion Criteria: * Histologically proven advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer * Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 * Received first-line treatment with a platinum-based regimen and had no evidence of disease ...
Trabectedin is an investigational small molecule being studied for the treatment of soft tissue sarcoma, including liposarcoma and leiomyosarcoma, as well as solid tumors and metastatic neoplasms. It is being developed by Johnson & Johnson (JNJ) and is currently in Phase 3 clinical trials.
Trabectedin is a small molecule that binds to the minor groove of DNA, interfering with cell division and transcription. It is being studied for its antitumor activity in soft tissue sarcomas, including liposarcoma and leiomyosarcoma.
Trabectedin is being developed by Johnson & Johnson, a pharmaceutical company listed on the New York Stock Exchange under the ticker symbol JNJ. The drug is currently in Phase 3 clinical development for oncology indications.
Trabectedin is in Phase 3 clinical development. It has completed two Phase 3 trials, including a study comparing trabectedin to dacarbazine in patients with advanced liposarcoma or leiomyosarcoma.
Trabectedin has been studied in clinical trials including NCT01343277, a Phase 3 trial in advanced liposarcoma or leiomyosarcoma, and NCT00072670, a Phase 2 trial in prostate cancer. These trials have been completed.
Yes, Trabectedin is also known as Yondelis. Clinical trials have used the name Yondelis to refer to trabectedin, such as in a Phase 2 study in prostate cancer and a Phase 1 safety study in soft tissue sarcoma.