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The European Network for Gynaecological Oncological Trial groups (ENGOT) is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Earlier, we reported on the ENGOT minimal requirements for trials between academic groups and pharmaceutical companies. In this paper, we summarize the roadmap for performing trials in the ENGOT framework. In this roadmap, we define how an ENGOT trial should be set up and discuss the following items: What are the conditions to classify a study as an ENGOT trial? What is an ENGOT protocol? How are an ENGOT protocol, informed consent (ICF), and case report form (CRF) produced? How is the center selection and feasibility performed in ENGOT trials? How are regulatory and operational tasks handled? How should a confidentiality agreement between the industry and the whole ENGOT network be negotiated? How are contracts made between the industry and ENGOT and between ENGOT groups? How are funding, insurance, and communication flow arranged in ENGOT trials? What are the requirements for conducting substudies and what are the tasks for the leading group in an ENGOT trial? A template of a confidentiality agreement, a checklist of ENGOT criteria for new study proposals, and guidelines for authorship are also provided.

Background Pegylated liposomal doxorubicin (PLD) is an established treatment for relapsed ovarian cancer. Preclinical and clinical evidences in other tumor types suggest that the proteasome inhibitor bortezomib can act synergistically with PLD. Methods Patients with relapsed ovarian cancer (N = 58), previously treated with platinum (100%) and taxane (95%), received bortezomib, 1.3 mg/m2 intravenous (days 1, 4, 8, and 11), and PLD, 30 mg/m2 intravenous (day 1), every 3 weeks. Tumor responses were assessed using Response Evaluation Criteria In Solid Tumors and Gynecologic Cancer Intergroup criteria. An optimal 2-stage design was implemented. Gene expression profiling in peripheral blood was characterized before and during treatment in 10 platinum-sensitive patients enrolled in stage 2 of the study. Results Median number of bortezomib-PLD cycles was 3.5. Of 38 patients in the platinum-sensitive group, 9 responses were observed (median duration, 4.8 months). The platinum-resistant group was closed at stage 1 owing to lack of response. Toxicity was moderate and mainly consisted of hematologic, gastrointestinal, and mucositis events. Of the total 58 patients, peripheral neuropathy was reported in 9 patients (none were grade 3). Transcription profiling identified the prevalence of genes associated with ribonucleoprotein complexes, RNA processing, and protein translation. The gene expression changes were more robust in patients who responded or had stable disease compared with patients who had progressive disease. Conclusions The combination of bortezomib and PLD was well tolerated, but the antitumor activity is insufficient to warrant further investigation in ovarian cancer.

Objective: To review the current status of large phase academic clinical trials for women with ovarian cancer, address cross-cutting issues, and identify promising areas for future collaboration. Methods: In May 2009, the Gynecologic Cancer Intergroup, which represents 19 Cooperative Groups conducting trials for women with gynecologic cancer, and the US National Cancer Institute convened a Clinical Trials Planning Meeting. Results: The topics covered included the impact of new developments in cancer biology upon molecular targets and novel agents, pharmacogenomics, advances in imaging, the potential benefit of diet and exercise to reduce the risk of recurrence, academic partnership with industry, statistical considerations for phases 2 and 3 trials, trial end points, and symptom benefit and health-related quality-of-life issues. The clinical trials discussed spanned the spectrum of ovarian cancer from initial diagnosis, staging, and cytoreductive surgery to consolidation chemotherapy, and treatment of recurrent disease. Conclusions: Ongoing and effective collaboration with industry, government, and patients aims to ensure that the most important scientific questions can be answered rapidly. We encourage women with ovarian cancer and their oncologists to consider participation in the academic clinical trials conducted by the member groups of the Gynecologic Cancer Intergroup.

Although less frequently than in older women, about 15% of invasive epithelial ovarian cancer may occur in young women, for whom preservation of fertility potential is an important clinical goal. We reviewed the published evidences from the European literature on the role of conservative surgery in women with invasive epithelial ovarian cancer. Three reports were identified from the Italian and French literature; the data were analyzed together with our own experience in terms of relapse rate, relapse in the preserved ovary, survival, and fertility outcome. A total of 152 conservative surgeries were reported: 88 patients with stage IA, 2 with stage IB, 51 with stage IC, 2 with stage II, 3 with stage IIIA, and 6 with stage IIIC. Relapses occurred in 18/152 patients (11.8%) and involved the preserved ovary in 11 cases (7%). Fifty-three pregnancies were recorded with 38 uneventful term deliveries, 2 ectopic pregnancies, 6 spontaneous abortions, 4 terminations, and 2 with unknown outcome. Nine patients (5.9%) have died of disease. These findings confirm that young women with stage I invasive epithelial ovarian cancer may receive a successful treatment of their disease without sacrificing fertility.