Trial reportCancer chemotherapy and pharmacology2012
Exposure-response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection.
Trial report in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00479817 (A Randomized, Double-Blind, Placebo Controlled, Phase 2 Trial of Paclitaxel in Combination With AMG 386 in Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo Controlled, Phase 2 Trial of Paclitaxel in Combination With AMG 386 in Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Angiogenesis inhibitors for the treatment of epithelial ovarian cancer.The Cochrane database of systematic reviews · 2023Pooled it
- Trial
- Exposure-Response and Tumor Growth Inhibition Analyses of the Monovalent Anti-c-MET Antibody Onartuzumab (MetMAb) in the Second- and Third-Line Non-Small Cell Lung Cancer.The AAPS journal · 2017Trial
- A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma.British journal of cancer · 2013Trial
- Trial
- Article
- Randomized Phase 2 Study of Trebananib (AMG 386) with or without Continued Anti-Vascular Endothelial Growth Factor Therapy in Patients with Renal Cell Carcinoma Who Have Progressed on Bevacizumab, Pazopanib, Sorafenib, or Sunitinib - Results of NCI/CTEP Protocol 9048.Kidney cancer (Clifton, Va.) · 2019Article
- Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Molecular Pathways: Deciphering Mechanisms of Resistance to Macrophage-Targeted Therapies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Review
- Mathematical models of the steps involved in the systemic delivery of a chemotherapeutic to a solid tumor: From circulation to survival.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Pharmacokinetic drug-drug interaction study of the angiopoietin-1/angiopoietin-2-inhibiting peptibody trebananib (AMG 386) and paclitaxel in patients with advanced solid tumors.Investigational new drugs · 2015Article
- New ways to successfully target tumor vasculature in ovarian cancer.Current opinion in obstetrics & gynecology · 2015Review
- A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.Clinical genitourinary cancer · 2014Article
- Angiogenesis and antiangiogenic agents in cervical cancer.OncoTargets and therapy · 2014Review
- Profile of trebananib (AMG386) and its potential in the treatment of ovarian cancer.OncoTargets and therapy · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo characterize exposure-response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies.
methodsA population pharmacokinetic model of AMG 386 (N = 141) was developed and applied in an exposure-response analysis using data from patients (N = 160) with recurrent ovarian cancer who received paclitaxel plus AMG 386 (3 or 10 mg/kg once weekly) or placebo. Reduction in the risk of progression or death with increasing exposure (steady-state area under the concentration-versus-time curve [AUC(ss)]) was assessed using Cox regression analyses. Confounding factors were tested in multivariate analysis. Alternative AMG 386 doses were explored with Monte Carlo simulations using population pharmacokinetic and parametric survival models.
resultsThere was a trend toward increased PFS with increased AUC(ss) (hazard ratio [HR] for each one-unit increment in AUC(ss), 0.97; P = 0.097), suggesting that the maximum effect on prolonging PFS was not achieved at the highest dose tested (10 mg/kg). Among patients with AUC(ss) ≥ 9.6 mg h/mL, PFS was 8.1 months versus 5.7 months for AUC(ss) < 9.6 mg h/mL and 4.6 months for placebo. No relationship between AUC(ss) and grade ≥ 3 adverse events was observed. Simulations predicted that AMG 386 15 mg/kg once weekly would result in an AUC(ss) ≥ 9.6 mg h/mL in > 90% of patients with median PFS of 8.2 months versus 5.0 months for placebo (HR [15 mg/kg vs. placebo], 0.56).
conclusionsIncreased exposure to AMG 386 was associated with improved clinical outcomes in recurrent ovarian cancer, supporting the evaluation of a higher dose in future studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.