Comparing treatment strategies for advanced prostate cancer

ANZadapt: Phase II Randomised Controlled Trial of Patient-specific Adaptive Versus Continuous Abiraterone or eNZalutamide in Metastatic Castration-resistant Prostate Cancer

This study is testing if a personalized treatment plan that includes taking breaks from hormone therapy can help men with advanced prostate cancer live better and longer compared to taking the medication every day.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 168 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Leiden University Medical Center (Academic / other)
• Drugs / interventions: denosumab, Radiation
• Locations: 19 sites (Albury, New South Wales and 18 other locations)
• Trial ID: NCT05393791 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include men aged 18 or older with confirmed metastatic castration-resistant prostate cancer who are currently undergoing androgen deprivation therapy.

Not a fit: Patients whose prostate cancer is not metastatic or who have not undergone androgen deprivation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the duration of effectiveness of hormone therapies in treating advanced prostate cancer.

How similar studies have performed: While the approach of adaptive therapy is gaining interest, this specific strategy of pause-and-restart has not been widely tested in previous studies.

Eligibility criteria

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 this trial is running

Albury, New South Wales and 18 other locations

• 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)
• Sunshine Coast University Hospital — Birtinya, Queensland, Australia (Recruiting)
• Mater Hospital Brisbane — South Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• ICON Cancer Centre — Adelaide, South Australia, Australia (Recruiting)
• Eastern Health Box Hill — Box Hill, Victoria, Australia (Recruiting)
• Fiona Stanly Hospital — Murdoch, Western Australia, Australia (Recruiting)
• Radboud Univeristy Medical Centre — Nijmegen, Gelderland, Netherlands (Recruiting)
• Spaarne Gasthuis — Hoofddorp, North Holland, Netherlands (Recruiting)
• Isala Ziekenhuis — Zwolle, Overijssel, Netherlands (Recruiting)
• Groene Hart Ziekenhuis — Gouda, South Holland, Netherlands (Recruiting)
• Leids Universitair Medisch Centrum — Leiden, South Holland, Netherlands (Recruiting)
• Meander Medical Centre — Amersfoort, Utrecht, Netherlands (Recruiting)
• University Medical Center Groningen — Groningen, Netherlands (Recruiting)

Study contacts

• Principal investigator: Tom van der Hulle, MD — Leiden University Medical Center
• Study coordinator: Tom van der Hulle, MD PhD

Conditions Prostatic Neoplasms, Castration-Resistant; Antineoplastic Agents, Hormonal; Evolution; Quality of Life; Prostatic Neoplasms, Castration-Resistant / drug therapy