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Prostatic Neoplasms, Castration-ResistantPhase 2ANZadaptNCT05393791

Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC

A Phase 2 study testing Patient-specific adaptive therapy, Abiraterone acetate and Enzalutamide in people with Prostatic Neoplasms, Castration-Resistant, run by Leiden University Medical Center at 19 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Patient-specific adaptive therapy, Abiraterone acetate and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
168 participants
Where
19 sitesin 2 countries
Study dates
10 Nov 2022to 10 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to provide informed consent;
  • Aged 18 or older;
  • Histologically or cytologically confirmed adenocarcinoma of the prostate;
  • 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;
  • Presence of metastatic disease on WBBS and/or CT-scan;
  • 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:
Show all 16Show fewer
  • 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
  • Radiographic PD on bone scintigraphy and/or CT-scan;
  • A PSA concentration of ≥2 ng/mL.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
  • Controlled symptoms (opioids for cancer related pain stable for >4 weeks, no need for urgent radiotherapy for symptomatic lesions);
  • Estimated life expectancy of ≥12 months;
  • Patient has archival prostate cancer tissue available and which he consents to share or is willing to undergo a new tumour biopsy;
  • 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;
  • Any other therapies for CRPC (excluding denosumab and bisphosphonates) have to be discontinued 3 weeks prior to study randomisation;
  • Able to swallow the study drug and comply with study requirements.

Who cannot join

  • Life-threatening or serious medical or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study;
  • 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;
  • Known or suspected brain metastasis or leptomeningeal disease;
  • Small-cell or neuroendocrine differentiation of prostate cancer;
  • Radiation therapy for treatment of the primary tumour within 3 weeks of screening visit;
  • Radiation or radionuclide therapy for treatment of metastasis within 3 weeks of screening visit, excluding radiation to reduce pain symptoms;
Show all 12Show fewer
  • History of uncontrolled seizures (if patient and investigator wish to choose treatment with enzalutamide)
  • Unstable symptomatic ischemic heart disease, ongoing arrhythmias or New York Heart Association (NYHA) Class III or IV heart failure;
  • Known HIV infection, active chronic hepatitis B or C;
  • Known gastrointestinal (GI) disease that could interfere with GI absorption/tolerance of study drugs;
  • 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.
  • 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.

Trial locations and contacts

19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Tom van der Hulle, MD PhD contact

0031715263464

t.van_der_hulle@lumc.nl

Samantha Oakes, Prof. contact

+61 2 90543600

trials@anzup.org.au

19 sites in 2 countries

Australia12 sites, 12 recruiting

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

    Hsiang Tan, +6170742336, hsiang.tan@sa.gov.au

    Recruiting

  • ICON Cancer Centre

    Adelaide, South Australia

    Sue Yeend, +61884740220, sue.yeend@icon.team

    Craig Gedye, A/Prof

    Recruiting

  • Border Medical Oncology Research Unit / The Border Cancer Hospital

    Albury, New South Wales, 2460

    Craig Underhill, cunderhill@bordermedonc.com.au

    Jacqui McBurnie, +61260641508, jacqui.mcburnie@bordermedonc.com.au

    Recruiting

  • Sunshine Coast University Hospital

    Birtinya, Queensland

    Christine Cook, +61752020651, SC-Oncologytrials@health.qld.gov.au

    Andrew Schmidt, Dr.

    Recruiting

  • Eastern Health Box Hill

    Box Hill, Victoria

    Kiko Liu, +61390952465, kiko.liu@monash.edu

    Iris Tung, dr.

    Recruiting

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

    Jacquie Harvey, MBBS FRACP, +61 2 8514 0194, Jacquie.Harvey@lh.org.au

    Prof. Lisa Horvath, Horvath

    Recruiting

  • St George Hospital

    Kogarah, New South Wales

    Raymund Austria, +61 2 9113 1111, RaymundGino.Austria@health.nsw.gov.au

    Carole Harris, dr.

    Recruiting

  • Fiona Stanly Hospital

    Murdoch, Western Australia, 6150

    Caroline Stone, +61 8 6152 6530, caroline.stone@health.wa.gov.au

    Dr Thomas Ferguson

    Recruiting

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

    Kim Adler, +612 40143282, kim.adler@calvarymater.org.au

    Howard Chan, Dr.

    Recruiting

  • Mater Hospital Brisbane

    South Brisbane, Queensland, 4101

    Donna Harvey, Donna.Harvey@mater.org.au

    Dr. Niara Oliveira

    Recruiting

  • Genesis Care North Shore

    St Leonards, New South Wales, 2065

    Grace Till, +61 474 164 541, Grace.Till@genesiscare.com

    Dr. Laurence Krieger, MBChB, FRACP

    Recruiting

  • Sydney Adventist Hospital

    Wahroonga, New South Wales, 2076

    Nina Singh, +61 2 9480 6280, nina.singh@sah.org.au

    Prof. Gavin Marx

    Recruiting

Other trials in Australia

Netherlands7 sites, 7 recruiting

  • Meander Medical Centre

    Amersfoort, Utrecht, 3813 TZ

    Joyce van Dodewaard - de Jong, MD PhD, 0031338507278, jm.van.dodewaard@meandermc.nl

    Joyce van Dodewaard - de Jong, MD PhD

    Recruiting

  • Groene Hart Ziekenhuis

    Gouda, South Holland, 2803 HH

    Wendy van der Deure, MD PhD, 0031182505005, Wendy.van.der.Deure@ghz.nl

    Wendy van der Deure, MD PhD

    Recruiting

  • University Medical Center Groningen

    Groningen, 9713 GZ

    Michel van Kruchten, MD PhD, m.van.kruchten@umcg.nl

    Michel van Kruchten, MD PhD

    Recruiting

  • Spaarne Gasthuis

    Hoofddorp, North Holland, 2134 TM

    Aart Beeker, MD PhD, 0031232245802, abeeker@spaarnegasthuis.nl

    Aart Beeker, MD PhD

    Recruiting

  • Leids Universitair Medisch Centrum

    Leiden, South Holland, 2333 ZA

    Tom van der Hulle, MD PhD, 0031715263464, t.van_der_hulle@lumc.nl

    Amy Rieborn, MD, 0031652887817, a.rieborn@lumc.nl

    Recruiting

  • Radboud Univeristy Medical Centre

    Nijmegen, Gelderland, 6525 GA

    Inge van Oort, MD PhD, 0031243613735, inge.vanoort@radboudumc.nl

    Inge van Oort, MD PhD

    Recruiting

  • Isala Ziekenhuis

    Zwolle, Overijssel, 8025 AB

    Metin Tascilar, MD PhD, m.tascilar@isala.nl

    Metin Tascilar, MD PhD

    Recruiting

Other trials in Netherlands

About this study

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

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.

Read the detailed description

Abiraterone and enzalutamide (AA/ENZ) are drugs which are being used to treat metastatic prostate cancer. These drugs are a form of additional hormonal therapy and have been used for many years. For most patients, these drugs work well and the prostate cancer stays under control for several months to years. In all patients, there will be a moment when the prostate cancer doesn't respond anymore to the treatment. This is called resistance. This leads to increasement of PSA, tumor growth on the CT-scan and/or bone scan or decline of condition. The investigators want to establish if it is possible to delay the development of resistance by using the drugs differently. It is now recommended to use AA/ENZ daily until the prostate cancer doesn't respond anymore to the treatment. During treatment, all cancer cells sensitive to treatment will die and all cells resistant for treatment will survive. Based on evolutionary principles, this might not be a wise strategy. The groups of resistant cancer cells will prevail and will grow faster and faster. This will lead to increasement of PSA, tumor growth on the CT-scan and/or bone scan or decline of condition. The investigators want to establish if it is better to not take the treatment drugs daily, but to pause the treatment on regular basis. The theory of the investigators is that, due to just in time pausing the treatment, a part of the treatment sensitive cells will remain alive. These treatment sensitive cancer cells will compete with the treatment resistant cells for limited space and nutrients. In this way, the treatment sensitive cancer cells prevent the accelerating growth of the treatment resistant cancer cells. Due to this phenomenon, the investigator hypothesis is the prostate cancer will respond longer to treatment. It will take longer until a new treatment is necessary or until a patients develops complaints. When the treatment is paused, patients might experience less side effects. It is easy to establish whether the prostate cancer responds to treatment by measuring PSA.

Being tested
Patient-specific adaptive therapy, Abiraterone acetate, Enzalutamide
Keywords
Antineoplastic Agents, Hormonal, Evolution, Quality of Life, Prostatic Neoplasms, Castration-Resistant / drug therapy
Medical subject headings
Prostatic Neoplasms, Castration-Resistant, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Patient-specific adaptive therapyOther

    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).

  • Abiraterone acetateDrug

    Also called Zytiga

    Use of abiraterone or enzalutamide

  • EnzalutamideDrug

    Also called Xtandi

    Use of abiraterone or enzalutamide

Study groups in NCT05393791
Study groupRoleWhat they receive
Experimental groupExperimentalIn 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.
Receives: Other: Patient-specific adaptive therapy; Drug: Abiraterone acetate; Drug: Enzalutamide
Control groupActive comparatorIn the control group, patients will receive the standard continuous treatment with abiraterone or enzalutamide (AA/ENZ) until criteria for treatment failure are met.
Receives: Drug: Abiraterone acetate; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to treatment failure

    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.

    Measured: 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 outcomes (8)

  1. Time to PSA progression while on treatment

    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.

    Measured: 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.

  2. Radiographic progression-free survival while on study treatment

    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.

    Measured: 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.

  3. Overall survival

    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.

    Measured: 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.

  4. Time to first skeletal-related event

    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.

    Measured: 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.

  5. Health Related Quality of Life - FACT-P

    FACT-P Quality of Life questionnaire

    Measured: FACT-P questionnaire will be obtained every 12 weeks up to 3 years after randomization

  6. Health Related Quality of Life - EQ-5D-5L

    EQ-5D-5L questionnaire.

    Measured: EQ-5D-5L questionnaire will be obtained every 12 weeks up to 3 years after randomization

  7. Health Related Quality of Life - Pain

    Pain score per Brief Pain Inventory.

    Measured: Brief Pain Inventory questionnaire will be obtained every 12 weeks up to 3 years after randomization

  8. Adverse events

    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.

    Measured: Adverse events will be measured every 12 weeks, up to 3 years after randomization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2022
  2. Study start10 Nov 2022
  3. Primary completion10 Nov 2027 (estimated)
  4. Study completion10 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Control group and experimental group
Masking
None (open label)
Enrolment
168 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05393791
Sponsor's protocol ID
79835
Other IDs
ANZUP 2101
Acronym
ANZadapt
Status last verified
Nov 2024
First submitted
18 May 2022
Last updated
26 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Patient-specific adaptive therapy, Abiraterone acetate and Enzalutamide in people with Prostatic Neoplasms, Castration-Resistant, run by Leiden University Medical Center at 19 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Australia, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tom van der Hulle, MD PhD (0031715263464, t.van_der_hulle@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to treatment failure (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05393791.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.

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