Dr. Nicolas Penel recently completed a Research Fellowship at EORTC Headquarters. During his stay he became involved in a number of studies and projects, particularly with projects being conducted by the EORTC Soft Tissue Sarcoma Group (STBSG), Brain Tumor Group (BTG), and Endocrine Tumors Task Force (ETF).
Work with the STBSG
Working with Martine Van Glabbeke, Assistant Director of the Independent Data Monitoring Committee Unit, and Monia Ouali, junior statistician in the Statistics Department, and in collaboration with Véronique Brouste and Simone Mathoulin-Pelissier of the Department of Biostatistics at the Institut Bergonié, Dr. Penel was involved in developing and validating two predictive models for early death in patients with metastatic soft tissue sarcomas. Two different methods, scoring based on logistic regression analysis and probability tree development (CHAID Analysis) were used in this work. These models were developed using the EORTC Database and validated with the French Sarcoma Group Database. Using these same databases, the predictive factors for overall survival in patients with metastatic soft tissue sarcomas and receiving combination chemotherapy were explored.
Another project involved the review all the trials published in the last ten years that concerned investigating second line treatment in patients with metastatic soft tissue sarcoma. The aim of this work was to generate new hypothesis for further trials in the STBSG. For the purpose of this work, the presented data were re-analyzed according the criteria of activity/inactivity defined by the STBSG. This study has been accepted for publications in Annals of Oncology.
In order to facilitate the design of further trials, literature data on a particular form of soft tissue sarcoma, angiosarcoma were reviewed, and this review has been accepted for publication in Critical Reviews in Oncology and Hematology.
Working with Sandrine Marreaud, Head of the EORTC Medical Department, Dr. Penel contributed to the development of several study protocols:
- Preparation of a substantial and scientific amendment for the EORTC 62063 trial: A phase III randomized study evaluating surgery of residual disease in patients with metastatic gastro-intestinal stromal tumor responding to Imatinib mesylate.
- Preparation of a substantial and scientific amendment for the EORTC 62072 trial: A randomized double blind phase III trial of Pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or following prior therapy.
- Participation in the full protocol review and preparation of materials for the investigator meeting held in June 2010 in Chicago for the EORTC 62091 trial: A phase IIb/III multicenter study comparing the efficacy of trabectedin administered as a 3-hour or 24 hour infusion to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma.
- Preparation of the Outline (synopsis) and literature review for the EORTC 62101 trial: A phase II multicenter study evaluating efficacy of pazopanib in patients with advanced bone sarcomas. This is a very complex trial, requiring, in absence of a solid literature, an innovative design based on Growth Modulation Index.
- Preparation of the outline submission to protocol review committee (PRC), the response to the PRC comments, full development of the EORTC 62092 trial: A phase III randomized study of pre operative radiation plus surgery versus surgery alone for patients with retroperitoneal sarcomas. The writing of this protocol required closed collaboration with the EORTC Quality Assurance in Radiotherapy Unit, the Pharmacovigilance Unit, and the Statistics Department. This phase III randomized trial requires several interim analyses for safety and needs an adaptation of the Vigilance Chapter for a better assessment and reporting of surgical morbidity. This work was done in collaboration with both study coordinators, Sylvie Bonvalot, Institut Gustav Roussy, and Rick Haas, The Netherlands Cancer Institute – Antoni van Leeuwenhoekziekenhuis.
Together with Jocelyne Flament, Head of the Translational Research and Imaging Department, Nicolas supported the development of the new template of Patient Information Sheet/Informed Consent.
Development of the EORTC 26091 study protocol: Randomized trial assessing the significance of Bevacizumab in recurrent grade II and Grade III gliomas. The TAVAREC trial, in collaboration with Denis Lacombe, EORTC Director, and Pr M Van den Bent, Erasmus University Medical Center, who is the Study Coordinator.
He also lent a hand in setting the groundwork for the Endocrine Tumors Task Force, and performed a literature review on adrenal gland tumors management and identification of potential biological target/innovative strategies, and contributed to the preparation of the SWOT analysis for the Adrenal Gland Tumor subcommittee with Jillian Harrison and Anne-Sophie Govaerts of EPOD, Ravi Karra, Medical Department, and Denis Lacombe.
Dr. Penel has taken a position as the Deputy Head of the General Oncology Department at the Centre Oscar Lambret in Lille, France, and intends to stay in touch with the EORTC, especially with the Soft Tissue and Bone Sarcoma Group and the Endocrine Tumors Task Force. He plans to undertake collaborative work with the EORTC concerning prognostic factors for early death in patients enrolled in phase I trials, and, during the past Flims Workshop, he prepared a study protocol (Activity and safety of 2 strategies, doxorubicin alone followed by pazopanib at progression or pazopanib followed by doxorubicin alone at progression, in chemo-naïve patients with metastatic non-adipocytic sarcomas: a phase II randomized non-comparative study of the EORTC Sarcoma Group) that will be presented to the EORTC ExCo. He is also actively pursuing discussions with several pharmaceutical companies that develop anti-some angiogenic agents in order to develop an angiosarcoma study.