International clinical studies
Many renowned medical centres all over the world, specialising in diagnostics and treatment of prostate cancer, participate in clinical studies concerning this cancer. Urologists and oncologists at the best medical centres in Europe and the United States are still looking for even better and more modern methods for prostate cancer treatment.
HIFU CLINIC Prostate Cancer Treatment Centre and medical centres cooperating with it participate in enrolment of patients for those most modern treatment methods under clinical studies. Recently, many of them concern use of immunotherapy for prostate cancer treatment. It should be noted that participation in clinical studies provides access to therapies that usually are available in the market after many years, and their prices may reach even several hundred thousand zlotys per therapy cycle. Participation in clinical studies is strictly governed by law and regulations of ethics committees, to ensure all patient's rights are observed. Participation in clinical studies is always free and use of a given therapy can be stopped at any stage of the protocol.
Please, arrange a consultation for initial assessment of a possibility for a patient to participate in clinical studies conducted in Poland and abroad.
GVAX-Pca® is one of vaccines obtained from prostate cancer cells. Due to genetic engineering they secrete GM-CSF. In this case, whole cancer cells are an antigen, which following a presentation by antigen presenting cells (APCs) stimulates immunological response involving T-cells and macrophages.
The Phase II of the clinical study of the GVAX-Pca® formulation proved immunogenicity, clinical activity and safe profile of this vaccine. Patients receiving GVAX had reduced levels of markers associated with osteoclastic activity (metastases to bones) and their time to disease progression was longer. It was also proven that therapy with GVAX-Pca® prolongs survival with an effect proportional to the dose. What is important, a risk of adverse effects does not change significantly with an increase in the dose. Side effects noted by patients included infectious reaction at the injection site and a sense of weariness.
Studies on the GVAX-Pca formulations are in progress. Also combining of this vaccine with other formulations, including chemotherapeutics, is considered.
Sipuleucel-T (Provenge®) belongs to formulations registered by the U.S. Food and Drug Administration (FDA) for treatment of asymptomatic or mildly symptomatic castrate-resistant prostate cancer. The aim of the Sipuleucel-T vaccine is to stimulate T-cells reaction against prostate cancer cells. It is administered as 3 injections, every 2 weeks. Sipuleucel-T (Provenge®) has an individual effect in each patient and must be prepared specially. The immune system searches for cancer cells in the patient's body and then destroys them.
Phase III of the clinical studies on the Sipuleucel vaccine versus placebo showed:
- longer total survival of patients, by ca. 4 months (3.9 to 4.3 months, depending on the study);
- low percentage of adverse effects; they were mainly of flu-like nature (shivering, headache, subfebrile condition);
- increased probability of survival for 36 months, by 8.7% (31.7% vs. 23%).
- Studies on this medicinal product imply permanent treatment results observed in patients even for 26 weeks after treatment initiation.
In the modern urology, treatment by immunotherapy involves use of formulations with viral vectors. Vaccine of this type results in a controlled "infection" stimulating the immune system against cancer cells. Main advantages of use of whole viruses in vaccines include exploiting natural viral immunogenicity and a possibility to use a high level of gene expression.
The PROSTVAC® vaccine is based of viruses from the Poxviridae family. Those viruses contain DNA of human PSA protein and 3 co-stimulating agents (including GM-CSF) of importance for stimulation of the immunological response.
In Phase I clinical studies, the PROSTVAC® vaccine showed immunological activity combined with a safe clinical profile. Phase II studies brought new positive results indicating prolonged time to PSA progression and prolonged survival in majority of patients. Currently, Phase III study is in progress with patients with asymptomatic or mildly symptomatic castrate-resistant prostate cancer.
Dr Marek Filipek is a main investigator in one of the Polish centres conducting the PROSPECT study for the PROSTAVAC vaccine. Enrolment into this study is already over.
PSMA (prostate specific membrane antigen) is a glycoprotein found on a surface of a cell membrane in prostate cells, both normal and cancer ones. When the antiandrogen therapy is initiated, PSMA expression increases.
J591 is a monoclonal antibody directed against the external PSMA domain. It is postulated to use radionuclides binding to J591 for therapeutic purposes. In phase II of the clinical study on radioactive lutetium bound to J591 involving 30 patients, a reduction of PSA levels by > 50% was observed in 10% of patients, and by 30% in 30% of patients. The most commonly observed adverse effect was thrombocytopenia. Currently phase II study is in progress in a group of patients with high risk castrate-resistant prostate cancer and biochemical progression. PSMA is of increasing importance in prostate cancer diagnostics.
ANTIBODIES – IPILIMUMAB®
Ipilimumab® is a human anti CTLA-4 monoclonal antibody. Blocking of this receptor may inhibit T-cells activity and enhance reaction against cancer cells in the prostate. Phase I clinical study on Ipilimumab in a group of 14 patients showed a long-term reduction in PSA by over 50% in 15% of patients.
Similar effectiveness was noted in Phase II clinical study evaluating this vaccine in monotherapy and in a combined therapy with docetaxel. Ipilimumab antibodies were also used in a combined therapy with the GVAX-Pca® vaccine, where efficacy of around 25% was achieved (PSA reduction by > 50%).
Previous clinical studies on this vaccine demonstrated a safe profile of its action. However, a high percentage of adverse effects was noted. The adverse effects of Ipilimumab administration included joint pain, muscle ache, sense of fatigue, nausea, diarrhoea, constipation, intestinal inflammation, hepatitis, adrenal insufficiency, and local reactions. Currently, enrolment to phase III study ended, to evaluate Ipilimumab efficacy versus placebo in patients with castrate-resistant prostate cancer after radiotherapy.