Journal article
A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies
Gynecologic oncology, Vol.121(3), pp.455-461
06/2011
DOI: 10.1016/j.ygyno.2011.02.013
PMCID: PMC3100412
PMID: 21414654
Abstract
<p><h3 id="x-x-S1title">Purpose</h3> <p id="x-x-P1">Protein kinase C (PKC) activation contributes to proliferation and angiogenesis in epithelial ovarian or primary peritoneal carcinoma (EOC/PPC). A multi-institutional phase II trial was conducted to evaluate the efficacy and safety of PKCβ inhibitor enzastaurin in persistent or recurrent EOC/PPC and to explore potential prognostic and predictive biomarkers. <h3 id="x-x-S2title">Methods</h3> <p id="x-x-P2">Eligible women with measurable platinum-sensitive and resistant EOC/PPC were treated with continuous administration of oral enzastaurin until disease progression or unacceptable toxicity. A two-stage sequential design was used to evaluate progression-free survival (PFS) ≥ 6-months, tumor response, and toxicity. Translational studies included sequencing of the <em>TP53</em>, <em>PTEN</em>, <em>PIK3CA</em> and <em>PKCβII</em> genes for somatic mutations, quantitative PCR assays for <em>AKT2</em> and <em>PTEN</em> copy number alterations, and measurement of circulating VEGF-A plasma levels. <h3 id="x-x-S3title">Results</h3> <p id="x-x-P3">Among 27 eligible and evaluable patients, 3 women with PFS ≥ 6-months (11%) and 2 women with partial responses (7%) were observed. One of them achieved a durable response and remains on the study. No grade 4 adverse events were observed. Most common grade 3 adverse events were constitutional (4) and gastrointestinal (3). Mutations in the <em>TP53</em> gene and abnormal copy number in the <em>PTEN</em> gene were common (56% and 48% of cases, respectively). <h3 id="x-x-S4title">Conclusions</h3> <p id="x-x-P4">Enzastaurin was tolerable but had insufficient activity to proceed with the second stage of accrual. However, 1 patient has been progression-free for 44 months. No association between a biomarker and response to enzastaurin has been found. <p id="x-x-P5">Exploratory analysis suggested an association between survival and <em>PTEN</em> copy number losses.</p>
Details
- Title: Subtitle
- A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies
- Creators
- Doris M. BenbrookJean A. HurteauDavid P. MichelinMichael W. SillLydia UshaAndrew K. GodwinRobert S. MannelKathleen M. DarcyKoen De Geest - University of IowaParviz Hanjani
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.121(3), pp.455-461
- DOI
- 10.1016/j.ygyno.2011.02.013
- PMID
- 21414654
- PMCID
- PMC3100412
- ISSN
- 0090-8258
- Comment
Supplementary materials available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100412/
This clinical trial was registered at www.clinicaltrials.gov, NCT 00407758.
The study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the GOG Tissue Bank (CA 27469, CA 11479) and the GOG Statistical and Data Center (CA 37517), CA 140323 and Ovarian Cancer Research Fund (to Dr. Andrew Godwin) and Eli Lilly Pharmaceutical Company. The following GOG member institutions participated in this protocol: Abington Memorial Hospital, University of Washington, University of Iowa Hospitals and Clinics, Rush-Presbyterian-St. Luke's Medical Center, University of Massachusetts Medical School, Fox Chase Cancer Center, University of Oklahoma and Community Clinical Oncology Program.
- Language
- English
- Date published
- 06/2011
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983557794802771
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