The study of pexidartinib and enzalutamide as a combined treatment in men with prostate cancer resistant to other treatments
- Conditions
- Prostate cancerCancerMalignant neoplasm of prostate
- Registration Number
- ISRCTN13103155
- Lead Sponsor
- niversity Hospital Southampton NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- Male
- Target Recruitment
- 100
1. Histologically or cytologically proven castrate resistant prostate cancer
2. Metastatic disease. Measurable or evaluable disease is acceptable
3. Serum testosterone <1.7 nmol/L (< 50 ng/dL)
4. No other current therapies for prostate cancer. Allowable exceptions are:
4.1. Use of an LHRH agonist or antagonist where required for ongoing androgen deprivation
4.2. Ongoing enzalutamide for patients entering the Dose Expansion Phase
4.3. Denosumab or bisphosphonates such as zoledronate or pamidronate
5. ECOG performance status 0 to 2
6. Haemoglobin = 8.5 g/dL; platelets = 100 x 109/L; neutrophils = 1.0 x109/L; INR = 1.5
7. 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
9. Able to swallow oral trial drugs without crushing
10. 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
11. 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)
12. Life expectancy > 3 months
13. Aged 16 years or over
14. Provision of written informed consent
Dose escalation phase:
Patients may be enzalutamide naive or refractory by either:
1. Commencing enzalutamide for the first time as a treatment for mCRPC as a result of entering this trial
1. Receiving retreatment with enzalutamide as a result of entering this trial providing a minimum of 12 weeks has elapsed since prior enzalutamide dosing. 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.
Dose expansion phase:
Patients will be enzalutamide refractory by either:
1. 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.
2. 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
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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method