TRINOVA‐2.
Study characteristics | ||
Methods | Randomised, double‐blind, placebo‐controlled phase 3 study from April 2011 to October 2013 in 69 sites in 16 countries (USA, Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hong Kong, Hungary, Italy, New Zealand, Poland, Singapore, Slovakia, Switzerland, Taiwan, UK) | |
Participants | 223 women with PR ROC Inclusion criteria Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube cancer ≥ 18 years of age One prior platinum‐based chemotherapeutic regimen for primary disease containing carboplatin, cisplatin, or another organoplatinum compound Radiographically documented disease progression Adequate bone marrow and organ function Exclusion criteria Platinum‐free interval > 12 months from their last platinum based therapy Major surgery within the last 4 weeks or still recovering from prior surgery Prior treatment with more than 3 regimens of anti‐cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer Prior treatment with PLD or any anthracycline‐based or mitoxantrone‐based chemotherapy CNS metastases |
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Interventions |
Intervention IV PLD 50 mg/m2 once every 4 weeks plus weekly IV trebananib 15 mg/kg Control IV PLD 50 mg/m2 once every 4 weeks plus weekly IV placebo |
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Outcomes |
Primary outcome PFS Secondary outcomes OS ORR DoR |
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Notes | ||
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Participants randomised, however method not specified |
Allocation concealment (selection bias) | Unclear risk | Allocation concealment for mentioned |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | Double blind, placebo controlled study |
Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not mentioned. Outcomes were assessed using the RECIST criteria. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Patient flow chart included and all patients accounted for. |
Selective reporting (reporting bias) | High risk | No study protocol available. Clinical trials.gov has only overall survival (OS) as secondary outcome. Overall response rate (ORR) and duration of response (DOR) are added as outcomes in results. |
Other bias | Unclear risk | Sponsored by Amgen, the maker of the study drug |
AE: adverse event; ALT: alanine amino transferase; ASCO: American Society of Clinical Oncology; AST: aspartate amino transferase; AUC: area under the curve; bd: twice daily; BEV: bevacizumab; BRCA: breast cancer antgen; CA125: cancer antigen 125; CAN: canfosfomide; CRs: complete responses; DCR: disease control rate; DoR: duration of response; DSMB: Data and Safety Monitoring Board; EC145: vintafolide; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; FR: folate receptor; GCIG: Gynecologic Cancer Intergroup; G‐CSF: granulocyte colony stimulating factor; GEM: gemcitabine; HQL: Health‐related quality of life assessment; HR: hazard ratio; IV: intravenous; IVI:intravenous infusion; M200: volociximab; NCI‐CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; NYHA: New York Heart Association; OLA: olaparib; ORR: objective (or overall) response rate; OS; overall survival; PAC: paclitaxel; PARP: Poly(ADP‐ribose) polymerase; PD: programmed death receptor; PDGF: platelet‐derived growth factor; PDGF‐R; platelet‐derived growth factor receptor; PD‐L: programmed death ligand; PFI: platinum‐free interval; PFS: progression‐free survival; PK: pharmacokinetic; PLD: peglyated liposomal doxorubicin; PPS; partially platinum‐sensitive; PR: platinum resistant (or refractory); PRs: partial responses; PS: platinum sensitive; PTT: prothrombin time; QoL: quality of life; RCT: randomised control trial; RECIST: Response Evaluation Criteria in Solid Tumours; ROC: recurrent/relpased ovarian cancer; SAE: serious adverse events; TBD: trabectedin; Tc: technetium; TOP: topotecan; TTP: time‐to‐progression; VTX‐2337: motolimod.