Contact information
Type
Public
Primary contact
Mrs Laura Alexander
ORCID ID
Contact details
CRUK Clinical Trials Unit
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
0141 301 7212
laura.alexander@glasgow.ac.uk
Additional identifiers
EudraCT number
2015-003720-32
ClinicalTrials.gov number
Protocol/serial number
SPECTRE2015
Study information
Scientific title
SPECTRE - Combined suppression of cholesterol bioavailability and androgen deprivation therapy to treat castration resistant prostate cancer: an interventional study
Acronym
SPECTRE
Study hypothesis
SPECTRE will establish whether inhibition of cholesterol biosynthesis in patients with ongoing ADT will suppress castration-resistant prostate cancer via a reduction in androgen mediated signalling.
Ethics approval
Not provided at time of registration
Study design
Single centre single arm phase II interventional study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet.
Condition
Castration resistant prostate cancer
Intervention
All eligible patients will receive a statin (Atorvastatin) to take orally for a 6 week period. Patients will be asked to attend the clinic once a week for 7 weeks, during the course of the trial. After completion of the trial medicine patients will attend for a further clinic visit, four weeks later. During each clinic visit, patients will be checked to ensure they are well, any side effects will be monitored and a blood test will be performed. Patients will also be asked to provide consent for additional blood samples at each study visit. These samples will be analysed in order to develop highly specific tests that will track the status of prostate cancer. Patients may also be requested to provide consent for two biopsy samples of their tumour; one before starting the trial medication, and another 5-7 weeks later. Biopsy samples will not be required from all patients taking part in the study.
Intervention type
Drug
Phase
Phase II
Drug names
Atorvastatin
Primary outcome measure
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
1. Maximum percentage drop in PSA, determined for each patient and presented in a waterfall plot.
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
Overall trial start date
01/07/2016
Overall trial end date
20/12/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
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
9. Willingness to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures
10. Ability to swallow oral medications
11. Willing to undergo two biopsies
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
40
Participant exclusion criteria
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)
Recruitment start date
20/12/2016
Recruitment end date
20/12/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Sponsor information
Organisation
NHS Greater Glasgow & Clyde
Sponsor details
Research & Development
NHS Greater Glasgow & Clyde
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Organisation
University of Glasgow
Sponsor details
Clinical Research & Development
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Prostate Cancer UK
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Intention to publish date
30/06/2021
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list