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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05393791




Registration number
NCT05393791
Ethics application status
Date submitted
18/05/2022
Date registered
26/05/2022
Date last updated
26/11/2024

Titles & IDs
Public title
Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC
Scientific title
ANZadapt: Phase II Randomised Controlled Trial of Patient-specific Adaptive Versus Continuous Abiraterone or eNZalutamide in Metastatic Castration-resistant Prostate Cancer
Secondary ID [1] 0 0
ANZUP 2101
Secondary ID [2] 0 0
79835
Universal Trial Number (UTN)
Trial acronym
ANZadapt
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Patient-specific adaptive therapy
Treatment: Drugs - Abiraterone acetate
Treatment: Drugs - Enzalutamide

Experimental: Experimental group - In the experimental group, treatment will be paused if there is a \>50% decline in baseline PSA. AA/ENZ will be restarted if the PSA rises to the same level or higher than the pre-treatment PSA. AA/ENZ treatment will be paused again after the PSA declines \>50% from the baseline. This pause/restart cycle of adaptive therapy will be repeated presuming consent, tolerance and safety. Patients who do not have a \>50% decline of their baseline PSA level after restarting AA/ENZ remain on treatment until the criteria for treatment failure are met.

Active comparator: Control group - In the control group, patients will receive the standard continuous treatment with abiraterone or enzalutamide (AA/ENZ) until criteria for treatment failure are met.


Other interventions: Patient-specific adaptive therapy
Patients will start taking abiraterone or enzalutamide (AA/ENZ) daily. PSA will be measured every month as well as radiological evaluation by CT-scan and bone scan. Treatment will be continued until PSA has dropped \>50%. The treatment will then be paused. Once the PSA has risen again above the pretreatment baseline, treatment will be re-initiated. AA/ENZ will be stopped again after the PSA declines \>50% from the baseline. This will be continued until criteria for treatment failure are met (death by any cause or at least 2 out of 3 of the following events while on treatment: radiographic progression on CT-scan and/or bone scan, PSA progression or clinical progression).

Treatment: Drugs: Abiraterone acetate
Use of abiraterone or enzalutamide

Treatment: Drugs: Enzalutamide
Use of abiraterone or enzalutamide
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to treatment failure
Timepoint [1] 0 0
Time from randomization until death by any cause, or until criteria for treatment failure are met. PSA progression and clinical progression will be measured every 4 weeks, radiographic progression every 12 weeks, both up to 3 years after randomization.
Secondary outcome [1] 0 0
Time to PSA progression while on treatment
Timepoint [1] 0 0
Time from randomization until an increase of PSA of >25% and >2 ng/mL persisting while a patient is on consecutive treatment for at least 8 weeks or death. PSA will be measured every 4 weeks until 3 years after randomization.
Secondary outcome [2] 0 0
Radiographic progression-free survival while on study treatment
Timepoint [2] 0 0
Time from randomization to death or the first occurrence of radiographic progression while a subject received treatment between the imaging tests. Bone scan and CT-scan will be measured every 12 weeks until 3 years after randomization.
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Time from randomization to the date of death due to any cause. Measured every 4 weeks up to 3 years after randomizaton and after end of treatment visit every 6 months until 2 years after end of treatment visit.
Secondary outcome [4] 0 0
Time to first skeletal-related event
Timepoint [4] 0 0
Time from randomization to first skeletal-related event or death. Bone scan and CT-scan will be measured every 12 weeks up to 3 years after randomization.
Secondary outcome [5] 0 0
Health Related Quality of Life - FACT-P
Timepoint [5] 0 0
FACT-P questionnaire will be obtained every 12 weeks up to 3 years after randomization
Secondary outcome [6] 0 0
Health Related Quality of Life - EQ-5D-5L
Timepoint [6] 0 0
EQ-5D-5L questionnaire will be obtained every 12 weeks up to 3 years after randomization
Secondary outcome [7] 0 0
Health Related Quality of Life - Pain
Timepoint [7] 0 0
Brief Pain Inventory questionnaire will be obtained every 12 weeks up to 3 years after randomization
Secondary outcome [8] 0 0
Adverse events
Timepoint [8] 0 0
Adverse events will be measured every 12 weeks, up to 3 years after randomization.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
10/11/2027
Actual
Sample size
Target
168
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit / The Border Cancer Hospital - Albury
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [5] 0 0
Genesis Care North Shore - St Leonards
Recruitment hospital [6] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [7] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [8] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
ICON Cancer Centre - Adelaide
Recruitment hospital [11] 0 0
Eastern Health Box Hill - Box Hill
Recruitment hospital [12] 0 0
Fiona Stanly Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2460 - Albury
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
- Kogarah
Recruitment postcode(s) [4] 0 0
2298 - Newcastle
Recruitment postcode(s) [5] 0 0
2065 - St Leonards
Recruitment postcode(s) [6] 0 0
2076 - Wahroonga
Recruitment postcode(s) [7] 0 0
- Birtinya
Recruitment postcode(s) [8] 0 0
4101 - South Brisbane
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
- Adelaide
Recruitment postcode(s) [11] 0 0
- Box Hill
Recruitment postcode(s) [12] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Gelderland
Country [2] 0 0
Netherlands
State/province [2] 0 0
Noord-Holland
Country [3] 0 0
Netherlands
State/province [3] 0 0
Overijssel
Country [4] 0 0
Netherlands
State/province [4] 0 0
Utrecht
Country [5] 0 0
Netherlands
State/province [5] 0 0
Zuid-Holland
Country [6] 0 0
Netherlands
State/province [6] 0 0
Groningen

Funding & Sponsors
Primary sponsor type
Other
Name
Leiden University Medical Center
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Anticancer Fund, Belgium
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Hormone tablets, abiraterone (Zytiga®) and enzalutamide (Xtandi®) are approved to treat advanced prostate cancer. However, even if these drugs are helpful, their effectiveness usually diminishes over time. Small pilot studies have indicated that using hormone tablets sparingly, for just long enough to control the cancer, followed by a break in treatment and restarting them later, seems to improve how long hormone tablets can control the cancer. This study aims to find out if this pause/restart strategy is better than taking hormone tablets every day continuously. The study will include 168 people with metastatic castrate resistant prostate cancer in the Netherlands and Australia. Patients will be randomly 1:1 assigned between the control group and the experimental group. In the control group, patients will take the treatment with AA/ENZ every day until the prostate cancer doesn't respond anymore to the treatment. In the experimental group, patients will start with daily AA/ENZ until the PSA has declined for \>50%. The treatment will then be paused and monthly PSA measurements will be performed. The treatment will be re-initiated when the PSA has increased to the level of before starting treatment. The treatment will be continued daily until the PSA has again dropped for \>50%. This pause/restart cycle will be repeated until the prostate cancer doesn't respond anymore to the treatment.
Trial website
https://clinicaltrials.gov/study/NCT05393791
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tom van der Hulle, MD
Address 0 0
Leiden University Medical Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tom van der Hulle, MD PhD
Address 0 0
Country 0 0
Phone 0 0
0031715263464
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05393791