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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05393791
Registration number
NCT05393791
Ethics application status
Date submitted
18/05/2022
Date registered
26/05/2022
Date last updated
8/05/2023
Titles & IDs
Public title
Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC
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Scientific title
ANZadapt: Phase II Randomised Controlled Trial of Patient-specific Adaptive Versus Continuous Abiraterone or eNZalutamide in Metastatic Castration-resistant Prostate Cancer
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Secondary ID [1]
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ANZUP 2101
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Secondary ID [2]
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79835
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Universal Trial Number (UTN)
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Trial acronym
ANZadapt
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant
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Condition category
Condition code
Cancer
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Prostate
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Time to treatment failure
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Assessment method [1]
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Defined as the time from randomization until death by any cause, or the occurrence of =2 of the following events:
Radiographic progression according to RECIST 1.1 and/or PWCG3 criteria on the CT-scan and/or WBBS while a subject received treatment with AA/ENZ during the whole period between the imaging tests. NB: Radiologic progression while a subject is off treatment in the experimental arm will trigger the endpoint, but may be an indication to restart treatment and continue with the adaptive dosing strategy
PSA progression, defined as an increase of PSA of >25% and >2 ng/mL occurring while a patient is on consecutive treatment with AA/ENZ for at least 8 weeks.
Clinical progression in the judgment of the treating clinician occurring while a patient is on consecutive treatment with AA/ENZ for at least 8 weeks.
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Timepoint [1]
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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.
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Secondary outcome [1]
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Time to PSA progression while on treatment
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Assessment method [1]
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defined as the 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 (according to PCWG3 criteria) or death. Patients without documented PSA progression or have not died will be censored at the last known time that the patient was progression-free. Patients who are lost to follow up will be censored at their last assessment time. Patients who begin a new anticancer treatment and have not had documented PSA progression will be censored at their last assessment point prior to beginning their new treatment.
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Timepoint [1]
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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.
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Secondary outcome [2]
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Radiographic progression-free survival while on study treatment
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Assessment method [2]
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Defined as the time from randomisation to first occurrence of radiographic progression by PCWG3 criteria and/or RECIST 1.1 on the CT-scan and/or WBBS while a subject received treatment with AA/ENZ during the whole period between the imaging tests or death. Patients without documented disease progression or have not died will be censored at the last known time that the patient was progression-free. Patients who are lost to follow up will be censored at their last assessment time. Patients who begin a new anticancer treatment and have not had a documented treatment failure event will be censored at their last assessment point prior to beginning their new treatment.
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Timepoint [2]
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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.
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Secondary outcome [3]
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Overall survival
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Assessment method [3]
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defined as the time from randomization to the date of death due to any cause. For patients with no documented death by the end of the study, OS will be censored on the last date the patient was known to be alive. Patients who are lost to follow up will be censored at their last assessment time. Patients who begin a new anticancer treatment and have not had a documented treatment failure event will be censored at their last assessment point prior to beginning their new treatment.
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Timepoint [3]
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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.
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Secondary outcome [4]
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Time to first skeletal-related event
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Assessment method [4]
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Time from randomization to first skeletal-related event or death will be assessed. A skeletal-related event is defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of anti-neoplastic therapy to treat bone pain. Patients without documented skeletal-related event or have not died will be censored at the last known time that the patient was progression-free. Patients who are lost to follow up will be censored at their last assessment time. Patients who begin a new anticancer treatment and have not had a documented treatment failure event will be censored at their last assessment point prior to beginning their new treatment.
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Timepoint [4]
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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.
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Secondary outcome [5]
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Health Related Quality of Life - FACT-P
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Assessment method [5]
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FACT-P Quality of Life questionnaire
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Timepoint [5]
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FACT-P questionnaire will be obtained every 12 weeks up to 3 years after randomization
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Secondary outcome [6]
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Health Related Quality of Life - EQ-5D-5L
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Assessment method [6]
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EQ-5D-5L questionnaire.
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Timepoint [6]
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EQ-5D-5L questionnaire will be obtained every 12 weeks up to 3 years after randomization
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Secondary outcome [7]
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Health Related Quality of Life - Pain
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Assessment method [7]
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Pain score per Brief Pain Inventory.
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Timepoint [7]
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Brief Pain Inventory questionnaire will be obtained every 12 weeks up to 3 years after randomization
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Secondary outcome [8]
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Adverse events
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Assessment method [8]
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An adverse event is defined as any symptom, sign, illness, or untoward experience (including a clinically significant laboratory finding classified as Grade 3 or higher by the National Cancer Institute's Common Terminology Criteria for Adverse Events v5.0) that develops or worsens during the course of the study, whether or not the event is considered related to study drug. Such an event should be recorded as an adverse event only after the first dose of study drug is taken. Adverse events will be assessed every 12 weeks.
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Timepoint [8]
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Adverse events will be measured every 12 weeks, up to 3 years after randomization.
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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/L)); 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 =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; 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Males
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
10/11/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
10/11/2027
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Actual
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Sample size
Target
168
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
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Recruitment hospital [1]
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Border Medical Oncology Research Unit / The Border Cancer Hospital - Albury
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Recruitment hospital [2]
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Chris O'Brien Lifehouse - Camperdown
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Recruitment hospital [3]
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Calvary Mater Newcastle - Newcastle
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Recruitment hospital [4]
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Genesis Care North Shore - St Leonards
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Recruitment hospital [5]
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Sydney Adventist Hospital - Wahroonga
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Recruitment hospital [6]
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Mater Hospital Brisbane - South Brisbane
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Recruitment hospital [7]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [8]
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Fiona Stanly Hospital - Murdoch
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Recruitment postcode(s) [1]
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2460 - Albury
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Recruitment postcode(s) [2]
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2050 - Camperdown
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Recruitment postcode(s) [3]
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2298 - Newcastle
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Recruitment postcode(s) [4]
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2065 - St Leonards
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Recruitment postcode(s) [5]
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2076 - Wahroonga
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Recruitment postcode(s) [6]
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4101 - South Brisbane
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Recruitment postcode(s) [7]
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5000 - Adelaide
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Recruitment postcode(s) [8]
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6150 - Murdoch
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Recruitment outside Australia
Country [1]
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Netherlands
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State/province [1]
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Gelderland
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Country [2]
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Netherlands
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State/province [2]
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Noord-Holland
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Netherlands
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State/province [3]
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Overijssel
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Country [4]
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Netherlands
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State/province [4]
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Utrecht
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Country [5]
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Netherlands
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State/province [5]
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Zuid-Holland
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Netherlands
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State/province [6]
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Groningen
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Funding & Sponsors
Primary sponsor type
Other
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Name
Leiden University Medical Center
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Australian and New Zealand Urogenital and Prostate Cancer Trials Group
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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Anticancer Fund, Belgium
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Address [2]
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Country [2]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05393791
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Tom van der Hulle, MD
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Address
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Leiden University Medical Center
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Tom van der Hulle, MD PhD
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Address
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Phone
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0031715263464
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05393791
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