Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC (ANZadapt)
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ClinicalTrials.gov Identifier: NCT05393791 |
Recruitment Status :
Recruiting
First Posted : May 26, 2022
Last Update Posted : May 8, 2023
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Condition or disease | Intervention/treatment | Phase |
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Prostatic Neoplasms, Castration-Resistant | Other: Patient-specific adaptive therapy Drug: Abiraterone acetate Drug: Enzalutamide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 168 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Control group and experimental group |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | ANZadapt: Phase II Randomised Controlled Trial of Patient-specific Adaptive Versus Continuous Abiraterone or eNZalutamide in Metastatic Castration-resistant Prostate Cancer |
Actual Study Start Date : | November 10, 2022 |
Estimated Primary Completion Date : | November 10, 2027 |
Estimated Study Completion Date : | November 10, 2027 |
Arm | Intervention/treatment |
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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.
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Other: 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). Drug: Abiraterone acetate Use of abiraterone or enzalutamide
Other Name: Zytiga Drug: Enzalutamide Use of abiraterone or enzalutamide
Other Name: Xtandi |
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.
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Drug: Abiraterone acetate
Use of abiraterone or enzalutamide
Other Name: Zytiga Drug: Enzalutamide Use of abiraterone or enzalutamide
Other Name: Xtandi |
- 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. ]
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.
- Time to PSA progression while on treatment [ Time Frame: 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. ]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.
- Radiographic progression-free survival while on study treatment [ Time Frame: 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. ]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.
- Overall survival [ Time Frame: 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. ]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.
- Time to first skeletal-related event [ Time Frame: 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. ]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.
- Health Related Quality of Life - FACT-P [ Time Frame: FACT-P questionnaire will be obtained every 12 weeks up to 3 years after randomization ]FACT-P Quality of Life questionnaire
- Health Related Quality of Life - EQ-5D-5L [ Time Frame: EQ-5D-5L questionnaire will be obtained every 12 weeks up to 3 years after randomization ]EQ-5D-5L questionnaire.
- Health Related Quality of Life - Pain [ Time Frame: Brief Pain Inventory questionnaire will be obtained every 12 weeks up to 3 years after randomization ]Pain score per Brief Pain Inventory.
- Adverse events [ Time Frame: Adverse events will be measured every 12 weeks, up to 3 years after randomization. ]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.
- Cost-effectiveness analysis [ Time Frame: QoL and adverse events will be measured every 12 weeks up to 3 years after randomization. Treatment duration will be evaluated every 4 weeks up to 3 years after randomization. ]A cost-utility analysis will be performed from a healthcare perspective. Medication and other hospital costs will be assessed from hospital registrations. Quality-adjusted life years (QALYs) will be estimated using the Dutch tariff for the EQ-5D-5L (and the EQ-VAS as secondary analysis). Costs and QALYs will be extrapolated to a life-long horizon.
- Cumulative duration on treatment [ Time Frame: Every 4 weeks up to 3 years after randomization ]defined as the number of weeks on active treatment from randomization to the occurrence of treatment failure while on treatment.
- Translational Biospecimens [ Time Frame: Baseline and every 12 weeks ]Plasma samples suitable for circulating tumour DNA (ctDNA) analyses will be collected. The aim would be to perform explorative analyses on ctDNA to understand mechanisms of resistance, predictors of occurrence of progressive disease, and whether these results support the eco-evolutionary dynamics theory.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | As the investigated disease is prostate cancer, only males are eligible for inclusion. |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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/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;
- Presence of metastatic disease on WBBS and/or CT-scan;
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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:
- 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 ≥10 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.
Exclusion Criteria:
- 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;
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05393791
Contact: Tom van der Hulle, MD PhD | 0031715263464 | t.van_der_hulle@lumc.nl | |
Contact: Margaret McJannett | +61 2 9046 8954 | trials@anzup.org.au |
Australia, New South Wales | |
Border Medical Oncology Research Unit / The Border Cancer Hospital | Recruiting |
Albury, New South Wales, Australia, 2460 | |
Contact: Craig Underhill cunderhill@bordermedonc.com.au | |
Contact: Jacqui McBurnie +61260641508 jacqui.mcburnie@bordermedonc.com.au | |
Chris O'Brien Lifehouse | Not yet recruiting |
Camperdown, New South Wales, Australia, 2050 | |
Contact: Jacquie Harvey, MBBS FRACP +61 2 8514 0194 Jacquie.Harvey@lh.org.au | |
Principal Investigator: Prof. Lisa Horvath, Horvath | |
Calvary Mater Newcastle | Recruiting |
Newcastle, New South Wales, Australia, 2298 | |
Contact: Kim Adler +612 40143282 kim.adler@calvarymater.org.au | |
Principal Investigator: A.Prof. Craig Gedye, MBChB FRACP | |
Genesis Care North Shore | Recruiting |
St Leonards, New South Wales, Australia, 2065 | |
Contact: Grace Till +61 474 164 541 Grace.Till@genesiscare.com | |
Principal Investigator: Dr. Laurence Krieger, MBChB, FRACP | |
Sydney Adventist Hospital | Not yet recruiting |
Wahroonga, New South Wales, Australia, 2076 | |
Contact: Nina Singh +61 2 9480 6280 nina.singh@sah.org.au | |
Principal Investigator: Prof. Gavin Marx | |
Australia, Queensland | |
Mater Hospital Brisbane | Recruiting |
South Brisbane, Queensland, Australia, 4101 | |
Contact: Donna Harvey Donna.Harvey@mater.org.au | |
Principal Investigator: Dr. Niara Oliveira | |
Australia, South Australia | |
Royal Adelaide Hospital | Recruiting |
Adelaide, South Australia, Australia, 5000 | |
Contact: Hsiang Tan +6170742336 hsiang.tan@sa.gov.au | |
Australia, Western Australia | |
Fiona Stanly Hospital | Recruiting |
Murdoch, Western Australia, Australia, 6150 | |
Contact: Caroline Stone +61 8 6152 6530 caroline.stone@health.wa.gov.au | |
Principal Investigator: Dr Thomas Ferguson | |
Netherlands | |
Radboud Univeristy Medical Centre | Recruiting |
Nijmegen, Gelderland, Netherlands, 6525 GA | |
Contact: Inge van Oort, MD PhD 0031243613735 inge.vanoort@radboudumc.nl | |
Principal Investigator: Inge van Oort, MD PhD | |
Spaarne Gasthuis | Not yet recruiting |
Hoofddorp, Noord-Holland, Netherlands, 2134 TM | |
Contact: Aart Beeker, MD PhD 0031232245802 abeeker@spaarnegasthuis.nl | |
Principal Investigator: Aart Beeker, MD PhD | |
Isala Ziekenhuis | Not yet recruiting |
Zwolle, Overijssel, Netherlands, 8025 AB | |
Contact: Metin Tascilar, MD PhD m.tascilar@isala.nl | |
Principal Investigator: Metin Tascilar, MD PhD | |
Meander Medical Centre | Recruiting |
Amersfoort, Utrecht, Netherlands, 3813 TZ | |
Contact: Joyce van Dodewaard - de Jong, MD PhD 0031338507278 jm.van.dodewaard@meandermc.nl | |
Principal Investigator: Joyce van Dodewaard - de Jong, MD PhD | |
Groene Hart Ziekenhuis | Not yet recruiting |
Gouda, Zuid-Holland, Netherlands, 2803 HH | |
Contact: Wendy van der Deure, MD PhD 0031182505005 Wendy.van.der.Deure@ghz.nl | |
Principal Investigator: Wendy van der Deure, MD PhD | |
Leids Universitair Medisch Centrum | Recruiting |
Leiden, Zuid-Holland, Netherlands, 2333 ZA | |
Contact: Tom van der Hulle, MD PhD 0031715263464 t.van_der_hulle@lumc.nl | |
Contact: Amy Rieborn, MD 0031652887817 a.rieborn@lumc.nl | |
Principal Investigator: Tom van der Hulle, MD PhD | |
University Medical Center Groningen | Not yet recruiting |
Groningen, Netherlands, 9713 GZ | |
Contact: Michel van Kruchten, MD PhD m.van.kruchten@umcg.nl | |
Principal Investigator: Michel van Kruchten, MD PhD |
Principal Investigator: | Tom van der Hulle, MD | Leiden University Medical Center | |
Study Chair: | A/Prof. Craig Gedye, MBChB,FRACP | Australian and New Zealand Urogenital and Prostate Cancer Trials Group | |
Principal Investigator: | Dr. Laurence Krieger, MBChB,FRACP | Australian and New Zealand Urogenital and Prostate Cancer Trials Group | |
Principal Investigator: | Dr. Amy Rieborn | Leiden University Medical Center |
Responsible Party: | dr. Tom van der Hulle, Principal Investigator, Leiden University Medical Center |
ClinicalTrials.gov Identifier: | NCT05393791 |
Other Study ID Numbers: |
79835 ANZUP 2101 ( Other Identifier: ANZUP ) |
First Posted: | May 26, 2022 Key Record Dates |
Last Update Posted: | May 8, 2023 |
Last Verified: | May 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Antineoplastic Agents, Hormonal Evolution Quality of Life Prostatic Neoplasms, Castration-Resistant / drug therapy |
Prostatic Neoplasms Prostatic Neoplasms, Castration-Resistant Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases |
Male Urogenital Diseases Abiraterone Acetate Antineoplastic Agents Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 Enzyme Inhibitors |