A Trial of Triamcinolone With a GnRH Analog for Castration Resistant Prostate Cancer

Castration resistant prostate cancer (CRPC) is a cancer which has become resistant to hormone therapy. Triamcinolone is a steroid drug, and it is hoped that when administered intra-muscularly with a gonadotropin-releasing hormone (GnRH) analog, it will reduce the tumours' ability to grow and thus improve the therapy response rate. This is a single arm, multi-centre phase II trial and it follows a Simon Two-stage minimax design based on the progression free survival rate at 6-months. A total of 41 patients will be recruited to the study. Following recruitment of the first 17 patients; an interim analysis will take place, and at least 7 of these will be required to have survived progression free, at 6 months in order to proceed to the 2nd stage of the trial. During the 2nd stage, if 20 or more patients out of the total 41 have survived progression free, then the drug will be developed further at a randomized phase II or phase III trial. Patients will receive monthly treatment of intramuscular triamcinolone and GnRH up until treatment failure (progression, toxicity or death) and survival information will then be collected. Patients will be identified through referrals and at multidisciplinary team meetings (MDTs). Eligible patients will be approached by members of the research team at outpatient clinic appointments. To be registered, the trial patients must satisfy all aspects of the eligibility criteria. Once an eligible patient is identified and prior to their participation in this study, the Investigator, or a person delegated by the Investigator will adequately explain the aims, methods, anticipated benefits, potential hazards, and relay the fact that should new safety information result in significant changes in the risk or benefit, study patients will be notified. The Investigator, or a person delegated by the Investigator must also explain to the patient that they are completely free to refuse to enter the study or to withdraw at any time during the study. The patient will be sent away with a patient information sheet and will be given at least 24 hours to consider study participation. If the eligible patient is satisfied and fully understands what the study entails and what is expected, written informed consent will be obtained and the patient will be registered into the trial. A blood test will be taken at 9am in the morning; the equivalent of 3 teaspoons of blood will be removed. The blood test will be used to assess blood circulating tumour cells (CTC), toxicity tumour markers, and the levels of cortisol and protein specific antigen (PSA is a chemical prostate cancer produces). A full history will be taken, and the patient will be examined. A bone scan performed prior to study participation as part of standard practice will also be assessed, providing it is not dated beyond a maximum of 6 weeks prior to the start of trial treatment. The inclusion and exclusion criteria will be verified once more. One day one, week one of treatment, the patient will be asked to return a 24 hour urine collection sample ( in order to obtain a profile of urinary steroids). The patient will receive an initial loading dose of 360 mg of triamcinolone, this will be administered over 3 injections (3 x 120 mg) into the muscle in the patient's buttocks. On day one, week four of treatment, the patient will receive only one injection of 120 mg IM of triamcinolone, and thereafter there will be one injection per treatment visit, four weekly until progression (as per day one, week four of treatment). Depending on the GnRH analog treatment the patient was on prior to the start of the trial, either 4 weekly or 12 weekly, it will remain the same for the duration of the patient's participation in the trial. The GnRH analog can be administered by their local GP as custom or if they are due receive the GnRH analog and triamcinolone at the same time, both will be administered at the site. However triamcinolone can be administered at the site only. The patient will be monitored with a follow up phone call from a nurse within a week following the first loading dose of triamcinolone, to see how the patient is and to check if there are any side-effects of the treatment. Three weeks following the start of treatment a blood test and 24-hour urine collection will be repeated. This is to assess whether the cancer is responding to treatment. These tests are also scheduled to be performed when the patient attends 4 weekly for triamcinolone treatment, however the doctor may request further tests depending on how the patient is responding to treatment. In particular, if PSA increases significantly while on treatment, the doctor may then decide to stop triamcinolone treatment and inform the patient of alternative treatment options. Following treatment failure, patients will be followed up every 3 months and permission will be sought to obtain patient survival data when they return to standard care appointments. An additional aspect of the study which is optional depending on the site and the patient is the translational research component: Provided the patient has not withheld consent, a blood sample will be taken at the start of the trial, following registration and another sample when treatment fails due to progression, which will then be used to analyse DNA mutations.