POLERISE - Peidartinib and Enzalutamide in metastatic castration resistant prostate cancer.

Phase 1

• Conditions: Metastatic Castration Resistant Prostate Cancer; MedDRA version: 21.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003291-47-GB
• Lead Sponsor: niversity Hospital Southampton NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-24
• Last Update Posted: 3 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 100

Inclusion Criteria

1. Histologically or cytologically proven castrate resistant prostate cancer
2. Metastatic disease. Measurable or evaluable disease is acceptable
3. In the dose escalation phase of the trial patients may be enzalutamide naive or refractory by either:

i.Commencing enzalutamide for the first time as a treatment for mCRPC as a result of entering this trial

ii.Receiving retreatment with enzalutamide as a result of entering this trial providing a minimum of 12 weeks has elapsed since prior enzalutamide. Prior enzalutamide in these circumstances may have been given for either hormone sensitive prostate cancer (for example within the STAMPEDE or ENZAMET clinical trials) or as a conventional treatment for mCRPC. There are no restrictions on other treatments used during this period. Such patients should have tolerated an enzalutamide dose of 160mg once daily

In the dose expansion phase of the trial patients will be enzalutamide refractory by either:

i.Currently receiving enzalutamide (for a minimum of 12 weeks) and with evidence of PSA and/or radiological progression according to RECIST 1.1 and PCWG3 criteria as judged by the investigator. These patients should have tolerated an enzalutamide dose of 160mg once daily. These patients may continue enzalutamide through the screening period.

ii.Have previously had evidence of PSA and/or radiological progression during a minimum of 12 weeks of enzalutamide treatment according to RECIST 1.1 and PCWG3 criteria as judged by the investigator. There are no restrictions on the time period since this prior use of enzalutamide or other treatments used during this period. These patients must have tolerated an enzalutamide dose of 160mg once daily. Where there has been a break of >8 weeks between prior enzalutamide and restarting it in this trial, patients will initially receive a four week run in period of single agent enzalutamide before commencing combination therapy to exclude a PSA response. Patients who exhibit a PSA decrease during the first four weeks will have the option to continue enzalutamide until the point of subsequent disease progression and could then enter the trial to commence combination therapy after discussion with the sponsor.

4.Serum testosterone <1.7 nmol/L (< 50 ng/dL)
5.No other current therapies for prostate cancer. Allowable exceptions are:

i.Use of an LHRH agonist or antagonist where required for ongoing androgen deprivation
ii.Ongoing enzalutamide for patients entering the Dose Expansion Phase
iii.Denosumab or bisphosphonates such as zoledronate or pamidronate

6.ECOG performance status 0 to 2
7.Haemoglobin = 8.5 g/dL; platelets = 100 x 109/L; neutrophils = 1.0 x109/L; INR = 1.5
8.Bilirubin = ULN; ALT and AST = 1.5 x ULN
9.For patients entering the Dose Expansion Phase of the trial: PSA of = 2 ng/mL
10.Able to swallow oral trial drugs
11.Able to safely provide both an archival formalin fixed paraffin embedded (FFPE) prostate cancer tissue sample and a prostate cancer fresh tissue sample from either the prostate or a metastatic site
12.Fertile men must agree to use a highly effective method of birth control while on study drug and up to 3 months after the last dose of study drug (see section 4.7)
13.Life expectancy > 3 months
14.Aged 16 years or over
15.Provision of written informed consent

Are the trial subjects under 18? yes
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 30
F.1.3 Elderly (>=65 years)

Exclusion Criteria

1.Patients with predominantly small cell or neuroendocrine differentiated prostate cancer
2.Administration of an investigational agent, chemotherapy or major surgery within 28 days of first dose of trial medication
3.Receiving a known CYP3A4 or CYP2C8 inducer or inhibitor (see appendix) within 2 weeks of starting trial treatment
4.Use of systemic corticosteroids within 2 weeks of starting trial treatment (topical and inhaled corticosteroids are acceptable)
5.Malabsorption syndrome, previous gastrointestinal surgery or other gastrointestinal condition that may affect drug absorption
6.Clinically significant cardiac arrhythmias including bradyarrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin)
7.Congenital long QT syndrome or patients taking concomitant medications known to prolong the QT interval
8.Patients with a prolonged QTc interval >480msec
9.History of clinically significant cardiac disease or congestive heart failure > New York Heart Association (NYHA) class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months
10.Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication
11.Patients taking warfarin. (Use of low molecular weight heparin is acceptable as an alternative for anticoagulation.)
12.For patients entering the Dose Expansion Phase of the trial: Prior malignancy with an estimated = 30% chance of relapse within 2 years in the view of the investigator with the exception of surgically treated basal or squamous cell carcinoma of the skin, melanoma in-situ or non-muscle invasive bladder cancer
13.History of seizures or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke, primary brain tumours, brain metastases or alcoholism
14.History of loss of consciousness within the previous 12 months
15.Known brain or leptomeningeal involvement
16.Unresolved clinically significant toxicity from prior therapy (except alopecia and grade 1 peripheral neuropathy)
17.Inability to comply with trial and follow up procedures

Study & Design

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