Comparing treatment strategies for advanced prostate cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial investigates the effectiveness of a patient-specific adaptive therapy approach versus continuous daily treatment with abiraterone and enzalutamide for patients with metastatic castration-resistant prostate cancer. The study aims to determine if a pause-and-restart strategy can delay the development of resistance to these hormone therapies, potentially improving patient outcomes. A total of 168 participants will be randomly assigned to either the control group, receiving daily treatment, or the experimental group, which will follow a tailored pause-and-restart regimen. The trial is being conducted in the Netherlands and Australia.

Why it matters

Who can join: the full rules

Inclusion 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:

   1. 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 progression after withdrawal (≥4 weeks since last flutamide or ≥6 weeks since last bicalutamide or nilutamide); OR
   2. Radiographic PD on bone scintigraphy and/or CT-scan;
7. A PSA concentration of ≥2 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; total bilirubin \< 1.5 times ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 3 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.

Exclusion Criteria:

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 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.

Where it's running

• Border Medical Oncology Research Unit / The Border Cancer Hospital
  Albury, New South Wales, Australia Recruiting
• Chris O'Brien Lifehouse
  Camperdown, New South Wales, Australia Recruiting
• St George Hospital
  Kogarah, New South Wales, Australia Recruiting
• Calvary Mater Newcastle
  Newcastle, New South Wales, Australia Recruiting
• Genesis Care North Shore
  St Leonards, New South Wales, Australia Recruiting
• Sydney Adventist Hospital
  Wahroonga, New South Wales, Australia Recruiting

Study contacts

• Principal investigator: Tom van der Hulle, MD — Leiden University Medical Center
• Study coordinator: Tom van der Hulle, MD PhD
• Email: t.van_der_hulle@lumc.nl
• Phone: 0031715263464

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Real-world patterns and outcomes in metastatic castration-resistant prostate cancer

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.