Table 2.
Characteristics of eligible studies
| ClincalTrials.gov identifier: NCT01846611/ET743-OVC-3006 | ||
| Study: Bradley J 2019 | ||
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| Methods | Phase 3 randomized, open-label, multicenter trial | |
| Study duration: May 2013 and April 2019 | ||
| Participants | 576 women with 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 progression for ≥ 6 months after the last dose | ||
| Received second-line treatment with a platinum-based regimen, with progression of disease after attaining a response | ||
| Progression of disease based on imaging after the second-line platinum-based regimen (individuals treated with a pegylated liposomal doxorubicin-containing regimen as a second-line therapy are eligible if subsequent disease progression occurs ≥ 9 months from the first dose) | ||
| Evidence of measurable disease at screening as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) | ||
| Participants no longer need to be able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid | ||
| Have a known BRCA 1/2 mutation status (for participants who do not have a known BRCA 1/2 status at screening, a blood sample will be collected to determine the status with the results available prior to randomization) | ||
| Laboratory values within protocol - defined parameters | ||
| Have left ventricular ejection fraction by multigated acquisition scan (MUGA) scan or 2D-ECHO within normal limits for the institution | ||
| Have side effects (except alopecia) of prior treatment resolved to at least Grade 1 according to the National Cancer Institute - Common Terminology Criteria of Adverse Events (NCICTCAE) (Version 4.0) | ||
| Have a negative urine or serum pregnancy test at screening | ||
| Agrees to protocol-defined use of effective contraception | ||
| Interventions | Experimental: Arm A: trabectedin + DOXIL (pegylated liposomal doxorubicin) | |
| 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 3 hours, 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 | ||
| Active Comparator: Arm B: DOXIL (pegylated liposomal doxorubicin) | ||
| Participants will receive DOXIL, 50 mg/m^2 administered as an IV infusion over approximately 90 minutes every 4 weeks | ||
| Outcomes | Primary Outcome Measures: Overall Survival (OS) | |
| Secondary Outcome Measures: Progression-Free Survival (PFS) and Objective Response Rate (ORR) | ||
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| Risk of bias | ||
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| Bias | Authors’ judgement | Support for judgement |
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| Random sequence generation | Unclear risk | No statement regarding method of random sequence generation provided |
| (selection bias) | ||
| Allocation concealment | Low risk | Individuals assigned to study treatment by chance |
| (selection bias) | ||
| Blinding of participants and personnel | High risk | Open - label (identity of assigned study drug will be known) |
| (performance bias) | ||
| Blinding of outcome assessment | Low risk | No statement regarding blinding of outcome assessment. However, the outcomes of interest were unlikely to be affected by lack of blinding of outcome assessor |
| (detection bias) | ||
| Incomplete outcome data | Low risk | Data analyses based on all participants |
| (attrition bias) | ||
| Selective reporting | Low risk | Data analyses based on all participants |
| (reporting bias) | ||
| Other bias | High risk | Data analysed according to an intention-to-treat basis |
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| ClincalTrials.gov identifier: NCT00113607/OVA-301 | ||
| Study: Bradley J 2010, Bradley J 2012, B.J 2015 | ||
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| Methods | Phase 3 randomized, open-label, multicenter trial | |
| Study duration: April 2005 to May 2007 | ||
| Participants | 672 women with Histologically proven epithelial ovarian cancer, epithelial fallopian tube cancer, or primary peritoneal cancer | |
| Prior treatment with only 1 platinum based chemotherapy regimen | ||
| Eastern Cooperative Oncology Group status of not more than 2 | ||
| Progression more than 6 months after the start of initial chemotherapy treatment | ||
| Interventions | Experimental: trabectedin + DOXIL (pegylated liposomal doxorubicin) | |
| 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 | ||
| Active Comparator: DOXIL (pegylated liposomal doxorubicin) | ||
| Monotherapy arm - DOXIL: 50 mg/m2 IV infusion over 90 minutes every 4 weeks | ||
| Outcomes | Primary Outcome Measures: Progression-Free Survival (PFS) | |
| Secondary Outcome Measures: Overall Survival (OS), Duration of Response, Median Area Under Curve (AUC) of Trabectedin, Median Maximum Plasma Concentration (Cmax) of Trabectedin and Objective Response Rate (ORR) | ||
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| Risk of bias | ||
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| Bias | Authors’ judgement | Support for judgement |
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| Random sequence generation | Unclear risk | No statement regarding method of random sequence generation provided |
| (selection bias) | ||
| Allocation concealment | Low risk | Study medication is assigned by chance |
| (selection bias) | ||
| Blinding of participants and personnel | High risk | Open - label (all people know the identity of the intervention) |
| (performance bias) | ||
| Blinding of outcome assessment | Low risk | No statement regarding blinding of outcome assessment. However, the outcomes of interest were unlikely to be affected by lack of blinding of outcome assessor |
| (detection bias) | ||
| Incomplete outcome data | Low risk | Data analyses based on all participants |
| (attrition bias) | ||
| Selective reporting | High risk | Data analyses based on all participants |
| (reporting bias) | ||
| Other bias | High risk | Data analysed according to an intention-to-treat basis |