Phase II randomised controlled trial of patient-specific adaptive versus continuous Abiraterone or eNZalutamide in metastatic castration-resistant prostate cancer: the ANZadapt study
- Conditions
- prostate cancerprostate carcinoma10038597
- Registration Number
- NL-OMON56330
- Lead Sponsor
- eids Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 84
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1. Willing and able to provide informed consent;
2. Aged 18 or older;
3. Histologically or cytologically confirmed adenocarcinoma of the prostate;
4. Ongoing androgen deprivation therapy with a GnRH analogue or bilateral
orchiectomy (i.e. surgical or medical castration with testosterone at screening
<=1.7 nmol/L (<0.5 ng/mL)); patients who have not had a bilateral orchiectomy,
must have a plan to maintain effective GnRH-analogue therapy for the duration
of the trial;
5. Presence of metastatic disease on WBBS and/or CT-scan;
6. Progressive disease at study entry defined as per PCWG3 as one or more of
the following criteria that occurred while the patient was on ADT:
a. PSA progression defined by a minimum of 2 rising PSA levels with an interval
of >=1 week between each determination. Patients who received an anti-androgen
must have PSA progression after withdrawal (>=4 6 weeks since last cyproterone,
flutamide, or >=6 weeks since last bicalutamide or nilutamide); OR
b. Radiographic PD on bone scintigraphy and/or CT-scan;
7. A PSA concentration of >=10 ng/mL.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
9. Controlled symptoms (opioids for cancer related pain stable for >4 weeks, no
need for urgent radiotherapy for symptomatic lesions);
10. Estimated life expectancy of >=12 months;
11. Patient has archival prostate cancer tissue available and which he consents
to share or is willing to undergo a new tumour biopsy;
12. Adequate organ function: absolute neutrophil count >1,500/µL (>1.5*109/L);
platelet count >100,000/µL (>100*109 /L), haemoglobin >90 g/L (>5.6 mmol/L);
total bilirubin <1.5 times ULN, alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) <2.5 times ULN; creatinine <175 µmol/L; albumin >30 g/L;
13. Any other therapies for CRPC (excluding denosumab and bisphosphonates) have
to be discontinued 3 weeks prior to study randomisation;
14. Able to swallow the study drug and comply with study requirements.
1. Life-threatening or serious medical or psychiatric illness that could, in
investigator's opinion, potentially interfere with participation in this study;
2. Diagnosis or treatment for another systemic malignancy within 2 years before
the first dose of study drugs. Potential participants with non-melanoma skin
cancer, non-muscle invasive bladder cancer, or carcinoma in situ of any type
are allowed if they have undergone complete resection;
3. Known or suspected brain metastasis or leptomeningeal disease;
4. Small-cell or neuroendocrine differentiation of prostate cancer;
5. Radiation therapy for treatment of the primary tumour within 3 weeks of
screening visit;
6. Radiation or radionuclide therapy for treatment of metastasis within 3 weeks
of screening visit, excluding radiation to reduce pain symptoms;
7. History of uncontrolled seizures (if patient and investigator wish to choose
treatment with enzalutamide)
8. Unstable symptomatic ischemic heart disease, ongoing arrhythmias or New York
Heart Association (NYHA) Class III or IV heart failure;
9. Known HIV infection, active chronic hepatitis B or C;
10. Known gastrointestinal (GI) disease that could interfere with GI
absorption/tolerance of study drugs;
11. Prior treatments with CYP17 inhibitors (e.g. ketoconazole) or novel
androgen receptor inhibitors (e.g. abiraterone, apalutamide, darolutamide or
enzalutamide). Bicalutamide, flutamide, cyproterone and nilutamide should be
stopped >6 weeks before screening visit. Prior treatment with docetaxel in the
mHSPC setting is allowed.
12. Any condition or reason that, in the opinion of the Investigator,
interferes with the ability of the patient to participate in the trial, which
places the patient at undue risk, or complicates the interpretation of safety
data.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of the study is TTTF while on treatment. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are TTPP while on treatment, rPFS, overall survival,<br />quality of life and health-economic cost consequences.</p>