SPECTREA single arm Phase II study to test if adding statins to hormone treatment will result in better cancer control in patients with hormone resistant prostate cancer.

Phase 1

Active, not recruiting

• Conditions: Castration Resistant Prostate Cancer; MedDRA version: 18.1Level: LLTClassification code 10007113Term: Cancer of prostateSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003720-32-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-02
• Last Update Posted: 20 July 2020

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Male
• Target Recruitment: 40

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:
a.Haemoglobin > 9.0 g/dL
b.Platelets > 100 x 109L
c.Creatinine <2 x ULN
d.Hepatic function: total bilirubin = 2 x ULN; ALT and AST = 3 x ULN
e.Creatine kinase ,= 5 x ULN
f.Fasting glucose = 5.6 mmol/L
g.Prothrombin time = 1.5 x ULN; APTT = 1.5 x ULN
h.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 for research purposes with a lesion (either primary or secondary) amenable to biopsy.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.
7) Administration of any investigational drug within 28 days of receiving the first dose of trial treatment
8) Major surgery within 28 days prior to trial entry
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 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)
14) Prior systemic therapy for CRPC with cytotoxic chemotherapy, abiraterone or enzalutamide. For clarity, docetaxel for non-castration resistant disease is permitted.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To explore the impact of atorvastatin on androgen receptor signalling in castration-resistant prostate cancer.;Secondary Objective: To study the impact of atorvastatin on the status of intermediates of androgen biosynthesis pathway in castration-resistant prostate cancer.;Primary end point(s): Assessment of the change in PSA levels from baseline during the treatment period, where a responder is any patient which achieves a =50% drop from baseline in PSA levels at any time over the 6-week period of statins treatment (PSA response). ;Timepoint(s) of evaluation of this end point: As above, the evaluation period will be the six week treatment period.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1)Maximum percentage drop in PSA level<br>2)Maximum change in testosterone level<br>3)Change in adrenal steroid DHEA (dehydroepiandrosterone) levels<br><br>;Timepoint(s) of evaluation of this end point: The evaluation period will be the six week treatment period, during which patients are evaluated weekly.