Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer

Karlan, Beth Y.; Oza, Amit M.; Richardson, Gary; Provencher, Diane; Hansen, Vincent; Buck, Martin; Chambers, Setsuko K.; Ghatage, Prafull; Pippitt, Charles H.; Brown, John V.; Covens, Allan; Nagarkar, Raj; Davy, Margaret; Leath, Charles A.; Nguyen, Hoang-Nam; Stepan, Daniel E.; Weinreich, David M.; Tassoudji, Marjan; Sun, Yu; Vergote, Ignace

doi:10.1200/jco.2010.34.3178

Cited by 195 publications

(116 citation statements)

References 30 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…Angiopoietins are circulating protein growth factors that promote angiogenesis by interacting with Tie2 receptors. The antiangiopoietin 1/2 peptibody, AMG386, given in combination with weekly paclitaxel demonstrated prolongation of PFS in a randomized phase II trial with recurrent ovarian cancer patients (30). Although several candidates are under evaluation, none of the molecules inhibiting NF-kB pathways have been used as an angiogenesis inhibitor in the clinical setting so far.…”

Section: Discussionmentioning

confidence: 99%

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

Kinose

Sawada

Makino

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by antiangiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost effective for use in all patients. Therefore, the development of a novel antiangiogenic drug, especially composed of smallmolecule compounds, could be a powerful armament for ovarian cancer treatment. As NF-kB signaling has the potential to regulate VEGF expression, we determined to identify whether VEGF expression is associated with NF-kB activation and to investigate the possibility of a novel IKKb inhibitor, IMD-0354 (IMMD Inc.), as an antiangiogenic drug. Tissue microarrays from 94 ovarian cancer tissues were constructed and immunohistochemical analyses performed. We revealed that IKK phosphorylation is an independent prognostic factor (PFS: 26

show abstract

Section: Discussionmentioning

confidence: 99%

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

Kinose

Sawada

Makino

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…One patient with refractory ovarian cancer in that study had a tumor reduction of 32.5% and a confirmed partial response (PR) at week 72; the patient withdrew from the study with a PR after 156 weeks of treatment. A phase 2 study suggested that patients with recurrent ovarian cancer receiving trebananib 3 mg/kg or 10 mg/kg once a week (QW) plus paclitaxel experienced longer PFS than patients receiving placebo QW plus paclitaxel [17]. In the randomized double-blind phase 3 TRINOVA-1 study, weekly trebananib 15 mg/kg combined with paclitaxel significantly improved PFS compared to weekly placebo combined with paclitaxel [18].…”

Section: Introductionmentioning

confidence: 99%

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Vergote

Schilder

Pippitt

et al. 2014

Gynecologic Oncology

Self Cite

View full text Add to dashboard Cite

Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.

show abstract

“…These changes are hypothesized to result in improved delivery of oxygen, nutrients, and cytotoxic chemotherapy to the tumor [43]. Table 1 details notable phase 2 studies of anti-angiogenesis therapy in EOC [44][45][46][47][48][49][50][51][52][53][54]. Of the 6 molecules studied, 5 have been advanced to the phase 3 arena.…”

Section: Phase 2 Studiesmentioning

confidence: 99%

Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

Eskander

Tewari

2014

Gynecologic Oncology

View full text Add to dashboard Cite

Randomized, Double-Blind, Placebo-Controlled Phase II Study of AMG 386 Combined With Weekly Paclitaxel in Patients With Recurrent Ovarian Cancer

Abstract: AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.

Cited by 195 publications

References 30 publications

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

Contact Info

Product

Resources

About