SPECTRE - Combined suppression of cholesterol bioavailability and androgen deprivation therapy to treat castration resistant prostate cancer

ISRCTN	ISRCTN16951765
DOI	https://doi.org/10.1186/ISRCTN16951765
EudraCT/CTIS number	2015-003720-32
Secondary identifying numbers	SPECTRE2015

Submission date: 16/02/2016
Registration date: 17/02/2016
Last edited: 16/05/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-using-a-drug-with-hormone-therapy-to-stop-prostate-cancer-from-spreading-spectre

Contact information

Mrs Laura Alexander
Public

CRUK Clinical Trials Unit
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Phone	0141 301 7212
Email	laura.alexander@glasgow.ac.uk

Study information

Study design	Single-centre single-arm Phase II interventional study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet.
Scientific title	SPECTRE - Combined suppression of cholesterol bioavailability and androgen deprivation therapy to treat castration resistant prostate cancer: an interventional study
Study acronym	SPECTRE
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	01/07/2016
Completion date	20/12/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target number of participants	40
Total final enrolment	14
Key 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
Key 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)
Date of first enrolment	20/12/2016
Date of final enrolment	20/12/2019

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

Beatson West of Scotland Cancer Centre

1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Sponsor information

NHS Greater Glasgow and Clyde
Hospital/treatment centre

Research & Development
NHS Greater Glasgow & Clyde
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
Scotland
United Kingdom

Website	http://www.nhsggc.org.uk/
"ROR"	https://ror.org/05kdz4d87

University of Glasgow
University/education

Clinical Research & Development
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
Scotland
United Kingdom

Funders

Funder type

Charity

Prostate Cancer UK
Private sector organisation / Other non-profit organizations

Alternative name(s): Prostate Cancer, Prostate Action, ProstateUK, prostatecanceruk
Location: United Kingdom

Results and Publications

Intention to publish date	30/06/2021
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		16/08/2020	16/06/2022	No	No
Plain English results			16/05/2024	No	Yes

Editorial Notes

16/05/2024: Cancer Research UK plain English results and total final enrolment added.
16/06/2022: EU Clinical Trials Register results added.
16/03/2020: Internal review.
17/07/2018: The intention to publish date has been changed from 31/08/2018 to 30/06/2021.
16/07/2018: The following changes have been made to the trial record:
1. The trial end date has been changed from 30/06/2018 to 20/12/2020
2. The recruitment start date has been changed from 01/07/2016 to 20/12/2016
3. The recruitment end date has been changed from 30/06/2018 to 20/12/2019
4. The participant inclusion criteria were updated
5. The participant exclusion criteria were updated
02/09/2016: Cancer Help UK lay summary link added.