NRG Oncology/GOG Studies
- The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.
- The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification.
- Endometrial carcinoma is the fourth most common malignancy among women world-wide and is the most common gynecologic cancer . Endometrial cancer is broadly categorized into three histologic types: endometrioid adenocarcinoma (EEA), accounting for up to 75% of cases, serous adenocarcinoma (ESA), accounting for an additional 20% of cases and carcinosarcoma (UCS), which makes up most of the remaining cases . In general, EEA has a better prognosis and a low recurrence risk, while ESA and UCS are more aggressive with accordingly worse prognosis and increased recurrence risk.
A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group studyAdvanced epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. Despite advances in surgical cytoreduction and chemotherapy, the five-year survival remains approximately 45.6% . Due to EOC being an immunogenic tumor, there has been significant interest in developing immunotherapy strategies using cytokines, monoclonal antibodies, checkpoint inhibitors, immune modulators, therapeutic vaccines, adoptive T cell transfer and oncolytic viruses.
- Ovarian cancer is the most lethal gynecologic cancer with over 22,000 new cases and 14,000 deaths in the United States per year ranking it fifth in cancer-related deaths for women . While the prognosis of ovarian cancer is recognized as poor, intraperitoneal (IP) chemotherapy has demonstrated a survival advantage in several Phase III clinical trials [2–4]. Most frequently cited is the Gynecologic Oncology Group (GOG) protocol 172 (GOG-172) which noted an increased median survival of 65.6 months in the IP arm compared to 49.7 months in the intravenous (IV) group (p = 0.03; RR 0.75 (0.58–0.97) .
- Intraperitoneal (IP) therapy improves survival compared to intravenous (IV) treatment for women with newly diagnosed, optimally cytoreduced, ovarian cancer. However, the role of IP therapy in recurrent disease is unknown. Preclinical data demonstrated IP administration of the proteasome inhibitor, bortezomib prior to IP carboplatin increased tumor platinum accumulation resulting in synergistic cytotoxicity. We conducted this phase I trial of IP bortezomib and carboplatin in women with recurrent disease.
- Endometrial cancer (EC) is responsible for ~76,000 deaths worldwide and has a higher incidence in developed countries due to its association with obesity . The majority of ECs are detected early (75%) and have a relatively good prognosis. However, if a patient presents with metastatic disease, or recurs after initial surgery, their prognosis is very poor, with a median survival of 7–12 months . Although the endometrioid histological subtype is associated with good prognosis compared to other subtypes, due to its prevalence it is still responsible for ~50% of all EC deaths.
- To examine the effect of celecoxib on cervical intraepithelial neoplasia 3 (CIN 3). This is a NRG Oncology/Gynecologic Oncology Group study with translational biomarkers.
- A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7 days delay in elderly ovarian cancer patients.
- The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS.
- This two-stage Phase II study assessed the activity of single agent alisertib in patients with recurrent/persistent uterine leiomyosarcoma (uLMS).
- Racial genetic admixture (RGA), a measure to account for ancestral genetic background that correlates with individual's racial classification, could provide insights on causation of racial disparity in endometrial cancer (EC). Our objective is to evaluate the association of RGA with EC outcomes.
- Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer.
- We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer.
- Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).