An open label phase I/randomised, double-blind phase II study in metastatic castration resistant Prostate Cancer of AZD5363 in combination with Docetaxel and prednisolone chemotherapy (ProCAID)

niversity Hospital Southampton NHS Foundation Trust0 个研究点目标入组 150 人开始时间: 2014年2月25日最近更新: 2021年7月21日

适应症

试验速览

阶段: 1 期
发起方
入组人数: 150

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

2017 Results article in https://www.ncbi.nlm.nih.gov/pubmed/28144789 Phase I results (added 31/07/2019) 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33326257/ results (added 21/01/2021)

研究设计

研究类型: Interventional

入排标准

性别: Male

入选标准

•Current inclusion criteria as of 31/07/2019:
•1. Histologically or cytologically proven mCRPC with documented metastases (measurable or evaluable disease is acceptable) now eligible for treatment with docetaxel chemotherapy
•2. Disease progression since the last change in therapy defined by one or more of the following according to the Prostate Cancer Working Group (PCWG2) criteria (J Clin Oncol 2008¿26:11481159):
•2.1. PSA progression as defined by the prostate cancer working group 2 (PCWG2) criteria (Scher et al. 2008 J Clin Oncol. 26; 1148). This must be based on a series of at least 3 readings at least 7 days apart demonstrating rising PSA. The 3rd reading must be = 2ng/ml If biochemical progression alone is to be used as the basis for determining disease progression (without radiographic or bone scan progression also). In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (i.e. the 3 readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy.
•2.2. Radiographic progression of nodal or visceral metastases as defined by RECIST version 1.1 (See Appendix 6)
•2.3. The appearance of two or more new bony metastases
•3. Serum testosterone <1.7 nmol/L (ongoing LHRH analogue or antagonist therapy is permitted to maintain a castrate state)
•4. Discontinuation of prior therapies for prostate cancer = 2 weeks prior to commencing study treatment (with the exception of an LHRH agonist or antagonist where required for ongoing testosterone suppression)
•5. No current anti-androgen withdrawal response from bicalutamide or flutamide. Consistent with PCWG2 guidelines, investigators should evaluate patients to exclude withdrawal response for 6 weeks after stopping bicalutamide or flutamide. Investigators need not wait to assess for withdrawal response in patients who did not respond, or who showed a PSA decline for = 3 months, after bicalutamide or flutamide was administered as a second-line or later intervention
•6. ECOG performance status 0 or 1
•7. Hb = 9g/dL¿ platelets = 100 x 109/L¿ neutrophils = 1.5 x109/L
•8. Bilirubin = ULN ¿ ALT and AST = 1.5 x ULN
•9. Sodium and potassium within the normal range for the site
•10. Able to swallow study drugs (without crushing/opening in the case of AZD5363)
•11. Life expectancy > 3 months
•12. Aged 18 years or over
•13. Provision of written informed consent
•Previous inclusion criteria:
•1. Histologically or cytologically proven mCRPC with documented metastases (measurable or evaluable disease is acceptable) now eligible for treatment with docetaxel chemotherapy
•2. Disease progression since the last change in therapy defined by one or more of the following according to the Prostate Cancer Working Group (PCWG2) criteria (J Clin Oncol 2008¿26:11481159):
•2.1. PSA progression as defined by the prostate cancer working group (2) (PCWG2) criteria (Scher et al. 2008 J Clin Oncol. 26¿ 1148). This must be based on a series of at least 3 readings at least 7 days apart. The 3rd reading must be >= 2ng/ml. In the event where an intermediate reading is lower than a

排除标准

•Current exclusion criteria as of 31/07/2019:
•1. Previous treatment with cytotoxic chemotherapy for castrate resistant prostate cancer. Patients may have received previous docetaxel for up to 6 cycles given in the ‘hormone sensitive setting’ or ongoing bisphosphonates or denosumab. There are no restrictions on prior use of second generation hormonal therapies e.g. abiraterone, enzalutamide as long as they have been discontinued > 2 weeks prior to commencing study treatment.
•2. Other prior malignancy with an estimated = 30% chance of relapse within 2 years
•3. Previously identified brain metastases, or spinal cord compression unless treated with full functional recovery
•4. Prior radiotherapy to > 30% of bone marrow
•5. Administration of an investigational agent within 30 days of first dose of study medication
•6. Patients will be excluded with any of:
•6.1. Diabetes mellitus type I
•6.2. Fasting plasma glucose [fasting is defined as no calorific intake for at least 8 hours] of either = 7.0mmol/L (126 mg/dL) for those patients without a pre-existing diagnosis of Type 2 diabetes mellitus or = 9.3 mmol/L (167mg/dL) for those patients with a pre-existing diagnosis of Type 2 diabetes mellitus
•6.3. Glycosylated haemoglobin (HbA1C) =8.0% (63.9 mmol/mol)
•6.4. Requirement for insulin for routine diabetic management and control
•6.5. Requirement for more than two oral hypoglycaemic medications for routine diabetic management and control
•7. Malabsorption syndrome, previous gastrointestinal surgery, or other gastrointestinal condition that may affect drug absorption
•8. Coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris or congestive heart
•failure (NYHA = grade 2) within the last 6 months
•9. Abnormal echocardiogram (LVEF 10.Uncontrolled hypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg)
•10. Uncontrolled hypotension (systolic blood pressure
•11. QTc interval of >480 msec at two or more time points within a 24 hour period
•12. Proteinuria (either 3+ on dipstick analysis or >500 mg/24 hours) or creatinine >1.5 x ULN concurrent with creatinine clearance
•13. Proteinuria (either 3+ on dipstick analysis or >500 mg/24 hours) or creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min (assessed as per local practice e.g. by Cockcroft and Gault estimation)
•14. Exposure to potent inhibitors or inducers of CYP3A4 or substrates of CYP3A4 and CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John’s Wort)
•15. Unresolved toxicity = grade 2 (except alopecia) from previous cancer therapy
•16. Patients with a partner of child-bearing potential who are not using a highly effective method of contraception, who are unwilling to use condoms during the study and for 30 days after the last dose of study drug
•17. Known hypersensitivity to AZD5363, its excipients, or drugs in its class
•18. Previous exposure to agents with the following mechanisms of action:
•18.1. Inhibition of AKT (e.g., MK2206, GDC0068, GSK2110183, GSK2141795) any inhibitor with PI3K ph

研究者

发起方

niversity Hospital Southampton NHS Foundation Trust

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