SPECTRE - Combined suppression of cholesterol bioavailability and androgen deprivation therapy to treat castration resistant prostate cancer
- Conditions
- Castration-resistant prostate cancerCancerProstate cancer
- Registration Number
- ISRCTN16951765
- Lead Sponsor
- HS Greater Glasgow and Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 14
Current participant inclusion criteria as of 16/07/2018:
1. Proven adenocarcinoma of the prostate, defined as:
1.1. Histological or cytological evidence of prostate cancer,
1.2. PSA > 100 at time of diagnosis and presence of more than 4 bone metastases
2. Disease progression despite on-going castration therapy (either using LHRH analogue or prior surgical orchiectomy (with or without abiraterone or enzalutamide) as judged by rising serial PSA measurements. This will be based on a series of at least 3 readings each taken at least 7 days apart. The 3rd reading must be = 2 ng/ml. 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). In patients who have received prior bicalutamide, flutamide or nilutamide, PSA progression must be proven after withdrawal of this drug.
3. Castrate levels of serum testosterone
4. Ongoing castration therapy (either LHRH analogue or prior orchiectomy, with or without abiraterone or enzalutamide). Please note, although the continuation of abiraterone or enzalutamide may be permitted, this must firstly be discussed with the chief investigator for approval, prior to study entry.
5. No therapy with statins or other cholesterol-lowering drug during a 28 day period prior to initiation of trial medication.
6. Male aged 18 or over
7. Life expectancy greater than 6 months
8. Adequate hepatic, bone marrow, coagulation and renal function as defined by the following criteria:
8.1. Haemoglobin = 9.0 g/dL
8.2. Platelets = 100 x 109L
8.3. Creatinine
8.4. Hepatic function: total bilirubin = 2 x ULN; ALT and AST = 3 x ULN
8.5. Creatine kinase = 5 x ULN
8.6. Prothrombin time = 1.5 x ULN; APTT = 1.5 x ULN
9. Willingness to comply with scheduled visits, medication plans and laboratory tests and other trial procedures
10. Ability to swallow oral medications
11. Willing to undergo two biopsies for research purposes with a lesion (either primary or secondary) amenable to biopsy
Previous participant inclusion criteria:
1. Histologically proven adenocarcinoma of the prostate (patients may or may not have evidence of metastatic disease)
2. Disease progression despite on-going castration therapy (either using LHRH analogue or prior surgical orchiectomy) as judged by rising serial PSA measurements: This will be based on a series of at least 3 readings each taken at least 7 days apart. The 3rd reading must be =2 ng/ml. 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). In patients who have received prior bicalutamide, flutamide or nilutamide, PSA progression must be proven after withdrawal of this drug
3. Castrate levels of serum testosterone (<1.7 nmol/l)
4. Ongoing castration therapy (either LHRH analogue or prior orchiectomy)
5. No therapy with statins or other cholesterol-lowering drug during a 2-month period prior to initiation of trial medication
6. Male aged 18 or over
7. Life expectancy greater than 6 months
8. Adequate hepatic, bone marrow coagulation and renal function as defined by the following criteria:
8.1.Haemoglobin > 9.0 g/dL
8.2.Platelets > 100 x 109L
8.3.Creatinine <2 x ULN
8.4.Hepatic function: total bilirubin = 2 x ULN; ALT and AST = 3 x ULN
8.5.Creatine kinase ,= 5 x ULN
8.6.Fasting glucose = 5.6 mmol/L
8.7.Prothrombin time = 1.5 x ULN; APTT = 1.5 x ULN
8.8. Platelets = 100
Current participant exclusion criteria as of 16/07/2018:
1. Uncontrolled hypertension (defined as systolic = 170 mmHg and/or diastolic = 100 mmHg, despite optimal therapy)
2. The requirement for strong opiates to control cancer related pain (codeine and tramadol are permitted)
3. NYHA class III or IV heart failure or Childs-Pugh liver failure class B or worse
4. Patients with symptomatic or radiographic disease progression (Note: Imaging studies will not be conducted specifically to meet this criterion but only if clinically indicated in accordance with standard of care)
5. Other severe or uncontrolled systemic disease or evidence of any other significant disorder or lab finding that makes it undesirable for the patient to participate in the trial
6. History of physical or psychiatric disorder that would prevent informed consent and compliance with protocol, or any psychological, familial, sociological or geographical consideration potentially hampering compliance with the trial protocol and follow up schedule.
7. Administration of any investigational drug within 28 days of receiving the first dose of trial medication
8. Major surgery within 28 days prior to trial registration
9. Active condition which affects drug absorption (e.g. prior gastrectomy or active peptic ulcer disease)
10. Planned change in systemic therapy for 6 weeks after study medication initiation
11. Planned requirement for radiotherapy or surgery for 6 weeks after study initiation
12. Prior hypersensitivity to atorvastatin or its constituents
13. Requirement for on-going anti-coagulant therapy (including heparins and warfarin)
Previous participant exclusion criteria:
1. Uncontrolled hypertension (defined as systolic = 170mmHg and/or diastolic = 100 mmHg despite optimal therapy)
2. The requirement for strong opiates to control cancer related pain; codeine and tramadol are
permitted
3. NYHA class III or IV heart failure or Childs-Pugh liver failure class B or worse
4. Patients with symptomatic or radiographic disease progression (Note: Imaging studies will not be conducted specifically to meet this criterion but only if clinically indicated in accordance with standard of care)
5. Other severe or uncontrolled systemic disease or evidence of any other significant disorder or lab finding that makes it undesirable for the patient to participate in the trial
6. History of physical or psychiatric disorder that would prevent informed consent and compliance with protocol, or any psychological, familial, sociological or geographical consideration potentially hampering compliance with the trial protocol and follow up schedule. Administration of any investigational drug within 28 days of receiving the first dose of trial treatment
7. Major surgery within 28 days prior to trial entry
8. Active condition which affects drug absorption (e.g. prior gastrectomy or active peptic ulcer disease)
9. Planned change in systemic therapy for 6 weeks after study initiation
10. Planned requirement for radiotherapy or surgery for 6 weeks after study initiation
11. Prior hypersensitivity to atorvastatin or its constituents
12. Requirement for on-going anti-coagulant therapy (including heparins and warfarin)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Achievement of =50% drop from baseline in PSA levels at any time over the 6-week period of statins treatment (PSA response). The proportion of patients achieving PSA response rate will be presented together with an 80% confidence interval computed using the Clopper-Pearson approach.
- Secondary Outcome Measures
Name Time Method 1. Maximum percentage drop in PSA, determined for each patient and presented in a waterfall plot. <br>2. Change in levels of a number of biomarkers (circulating and tissue) following treatment with trial agent, including circulating cell-free tumour DNA (ctDNA), gene expression and other markers such as CTCs and exosomes