Several clinical research projects will be performed by the participating institutions.
Contribution – LBI for Gynecology and Gynecologic Oncology
This institute is located at the Department of Obstetrics and Gynecology of the Medical University of Vienna (MUW) at the Allgemeines Krankenhaus (AKH) der Stadt Wien. During the last years the areas of interest were centered on projects relating to the characterization of clinical effects of genetic variants, i.e. polymorphisms, and the molecular detection and analysis of disseminated tumor cells in peripheral blood in gynecological malignancies.
Besides the close cooperation with the Molecular Oncology laboratory (head: Univ.-Prof. Dr. Robert Zeillinger) at the MUW the collaboration with the Department of Gynecology at the Charité Universitätsmedizin Berlin is noteworthy. Due to the membership in TOC (international Tumor bank Ovarian Cancer) there is access to biological specimens and clinical data of ovarian cancer patients.
The institute will contribute about 35 ovarian carcinoma patients for the tumor bank.
Contribution – LBI for Clinical Oncology and Photodynamic Therapy
Continuation of a clinical data base/epidemiologic information.
The assessment of scientific projects in oncology with regard to its clinical and socioeconomic relevance and their potential impact on clinical practice needs to consider epidemiologic data on incidence, age distribution and prognosis of malignant diseases. The LBI for Clinical Oncology and Photodynamic Therapy has a long lasting tradition in the collection of clinical data of patients with neoplastic disease that has been established as a source of epidemiologic information containing data from more than 10.000 patients. A major aspect of this information set is the fact that the collection of data reflects the clinical reality and is not biased by strict inclusion and exclusion criteria, which are used in most studies. For example analysis of the data from lung cancer patients collected since 1960 revealed a significant lack of progress in the treatment of this disease until recently. By means of this data collection it can be estimated how many patients could actually benefit from innovative diagnostic or therapeutic concepts emerging from the scientific activities of the LBI cluster. Furthermore the handling of the data of the ongoing clinical studies has been organized in such a way that they can be used in an anonymous form by the cluster.
Effect of innovative drugs on minimal residual disease (MRD)
At the 5th Department of Internal Medicine a number of clinical studies using new and innovative drugs are performed, partially in cooperation with the LBI for Applied Cancer Research. Thus MRD could be assessed in patients with malignant disease during treatment with new cytotoxic drugs, monoclonal antibodies, signal transduction inhibitors, cytokines and tumor vaccines. Using these activities the effect of these innovative drugs on the small and most critical cell population, responsible for the initiation and reinitiation of solid tumors can be studied. It is necessary to study the cell biology of the heterogeneous tumor cell populations and their chemosensitivity in order to check for the elimination of the most malignant and persistant tumor cell subpopulations.
Center of Excellence for neuroendocrine tumors
The highly variable clinical course of neuroendocrine tumors (NET) is histologically reflected by the recognition of low or high grade malignant tumors in the revised classification published by Capella et al. NET are also classified according to their site of origin and whether they are functional or non-functional. Functional tumors produce peptides that result in related symptoms, whereas non-functional tumors may either not produce any peptides or produce peptides (e.g. chromogranin) which do not induce any associated symptoms. Due to the different sites of origin NETs are diagnosed and treated by organ-specific and medical oncologists. In localized low grade NET surgery is the mainstay of therapy with curative intent whereas somatostatin analogs with or without interferon are therapeutic options for progressive low grade tumors.
There is general consense that chemotherapy is the treatment of choice for poorly differentiated tumors. These protocols are highly myelosuppressive and need special competence in the treatment of haematological toxicity. With these protocols remissions can be obtained in the majority of patients but unavoidably relapse occurs within a few months due to minimal residual disease. Therefore poorly differentiated NETs are an excellent model for studying MRD.
The 5th Department of Internal Medicinehas a long lasting tradition in treating NET from the lung since almost 20 years and is one of the leading centers in this field. Most recently encouraging results have been reported by us with dose-dense growth factor supported chemotherapy. Thus, this department has optimal clinical and scientific requirements to study MRD in NET.
In advanced stage, small cell lung cancer (SCLC) is characterized by an initial response to therapy followed by recurrence within approximately 1 year. The response rates to second-line therapies are low, resulting in a very poor survival rate. Due to these properties, primary tumor (biopsies) and recurrent tumors can be obtained and compared within a relatively short time period, facilitating analysis and investigation of circulating tumor cells. Since SCLC is linked to tobacco smoking the number of patients is increasing at a high level. The neuroendocrine markers (neuron-specific enolase, chromogranin etc.) expressed in SCLC may be suitable as markers for the detection of circulating tumor cells. Furthermore specific methylated gene sequences in serum can be used to indicate the presence of residual disease. At the 5th department of internal medicine approximately 20 patients with SCLC are newly treated each year and another 20 patients from other centers could be studied within the cluster. Tumor entities displaying similar neuroendocrine features are carcinoids and subpopulations of cells occurring in the development of hormone-independent prostate cancer. Other tumor entities are available at the hospital in Hietzing and the majority of samples can be obtained from the other participating LBIs.
Cooperations with other institutions (outside of the cluster).
The 5th Department of Internal Medicine is currently closely cooperating with a number of sites, which may be important for the project:
MRD in patients with acute leukaemia is assessed by immunophenotyping of blood and bone marrow samples by FACS at the Institute of Laboratory Medicine of the Hospital Hietzing;
MRD in patients with solid tumors is assessed by immunohistochemical methods in tissue biopsies at the Institute of Pathology of the Hospital Hietzing;
MRD in patients with NHL and AL is assessed by molecular methods in blood and bone marrow samples at the Instititute of Laboratory Medicine of the Medical University of Vienna;
MRD in patients with leukaemia is assessed by FISH in bone marrow samples at the Department of Hematology of the Hanusch Hospital;
MRD is assessed by monitoring tumor markers at the Institute of Laboratory Medicine of the Hospital Hietzing;
MRD is assessed by scan techniques at the Institute of Nuclear Medicine of the Hospital Hietzing.
LBI for Applied Cancer Research (LBI-ACR VIEnna)
The LBI-ACR VIEnna is a local research unit (study center) with strong international and European links. Since its foundation in 1993, the scientific orientation towards translational research in oncology, i.e. towards the area of preclinical research with mediate or immediate clinical realisation, which has been representing a long-time programmatic focus of the LBI-ACR VIEnna, has been maintained and even re-enforced over the years. The continuously increasing segment of the early drug developmental activities in form of clinical phase I-studies, especially those representing the first human experiences with molecules deriving from the preclinical developmental process represents this orientation described with utmost authenticity.
The institute covers areas of experimental diagnostic, clinical diagnostic, preclinical, early clinical and classical clinical research, epidemiologic and (chemo-) preventive research. The host organisation of the LBI-ACR VIEnna in form of the 3rd Medical Department – Center for Oncology and Haematology at the Kaiser Franz Josef-Spital represents with its access to patients the clinical base and is therewith a prerequisite for any translational research activity in this field. On the other side, there exists continuous integration of the consequences of the results obtained by clinical trials into the daily practice of the diagnosis and treatment of the patients at the host organisation.
There was/is persistent unlimited need for new effective, antitumoral substances with acceptable toxicity profile for i) reaching control of sensitive tumors, ii) maintaining control in stable disease and iii) reaching control of resistant/refractory tumors.
The priorities of the clinical study activities comprise the performance, the documentation and/or the evaluation of clinical trials of the phases I, II, III within the frame of international study groups such as the study groups of the European Organization for Research and Treatment of Cancer (EORTC) and the working groups of the CESAR Central European Society for Anticancer Drug Research-EWIV.
In cooperation with the Applied Cancer Research – Institution for Translational Research Vienna (ACR-ITR VIEnna), an international society integrating global and local research activities, and the CESAR Central European Society for Anticancer Drug Research-EWIV, a European society with preponderant activities within Central (Eastern) Europe, a host of clinical studies has been performed, including the newest drugs in cancer therapy. These three independent partners form a consortium, the Central European Anticancer Drug Development Platform (CEADDP), the (long-term) goal of which is the development of new anticancer agents and the clinical testing of new agents and/or antitumor principles with regard to their efficacy and safety in patients with malignant diseases. The testing and development of new antitumor substances is based on the most adequate scientific method, pharmacologic expertise, representing the state of the art with respect to science, ethics and law, respectively. In particular, Good Clinical Practice (GCP) according to the International Conference on Harmonisation (ICH) is considered.
In the frame of this “Strategisches Exzellenz Leitprojekt (SELP)”, CEADDP which is sponsored by the “Österreichische Forschungsförderungsgesellschaft (FFG)”, a cancer preventive trial has been established. Chemoprevention has been a long-term focus of research of the LBI-ACR VIEnna. Initially, preclinical work dealing with induction of differentiation with in vitro models dominated. Due to intensification of a collaboration with a long-term contractor of the LBI-ACR VIEnna (E. Schernhammer) who has profound expertise in epidemiologic research and has actually been working in one of the world most famous epidemiologic research teams at the Harvard University, research activities have been expanded to clinical work.
A topic of special long-term interest of the LBI-ACR VIEnna has been the one of the characterization of clonogenic/tumor stem cells. They are hypothesized to be the key cells responsible for maintenance, progression and ultimately, relapse of cancer. This renders them natural targets to research aiming at curing patients with malignancies.
In this cluster project, it is the goal of the LBI-ACR VIEnna to assess the antitumoral potential of all new substances, which are available within the frame of the clinical investigations in which the LBI-ACR VIEnna is involved, against circulating tumor cells/clonogenic cells/stem cells. The LBI-ACR VIEnna investigates the occurrence of circulating tumor cells/MRD in dependence of the different antitumoral therapeutics in order to select the most suitable drug for the (adjuvant) therapy of the respective tumor entity.
To establish in-vitro/in-vivo correlations for predefined/preselected tumor/tissue types and respective antitumoral substances
- in experimental clinical use (i.e. in use within clinical trials)
- in routine clinical use
To be reached within the (time-)frame of the cluster collaboration
Performance of in-vitro/in-vivo correlations
The performance of in-vitro/in-vivo correlations is based on a collaboration of clinical investigators with basic researchers/preclinical investigators and biostatistician(s). The performance of the clinical investigations will be done by the employees of the LBI-ACR VIEnna in collaboration with those of the other clinically oriented LBIs of the cluster. The performance of the preclinical investigations will be executed by the members/employees of the preclinically orientated LBIs of the cluster and the employee(s) of the LBI-ACR VIEnna.
- To make a rational indication for treatment and to perform a rational selection of therapy for adjuvant antitumoral treatment
- To be reached in a consecutive period of a cluster