Prostatic NeoplasmsPhase 2ADAMNCT04295447
Adjuvant Apalutamide in Subjects With High-risk Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy
A Phase 2 study testing Apalutamide 60Mg Tab in people with Prostatic Neoplasms, run by Universität Münster at 21 sites in 2 countries.
Trial summary
The primary objective of this trial is to determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE) in comparison to standard of care (SOC). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Apalutamide 60Mg Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 10 Dec 2020to 30 Nov 2028
- 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
- Signed informed consent form (ICF).
- Men ≥ 18 years of age.
- Patients with histologically confirmed adenocarcinoma of the prostate after radical prostatectomy.
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.
- Exclusion of metastatic disease by computed tomography (CT)-scan of abdomen (magnetic resonance imaging (MRI) of abdomen is possible) and bone scan prior to study inclusion. A PSMA PET-CT/MRI is possible. In this case it has to be done with a diagnostic CT/MRI with contrast media and not with a low dose CT-scan only. In case PSMA-PET imaging has been done, a bone scan can be omitted. CT/MRI, and bone-scan imaging or PSMA PET-CT/MRI administered ≤12 weeks before RPE may be used for screening.
- Patients after radical prostatectomy must meet the d'Amico criteria for high risk of disease recurrence: i.e. one of the following after RPE: 1) Gleason score ≥8, any T-stage, any initial PSA (iPSA) or 2) Gleason score 6 or 7, any iPSA and ≥pT3c or 3) iPSA >20 ng/ml, any Gleason score, any T-stage.
Show all 21Show fewer
- Patients have to have recovered from radical prostatectomy within four weeks to be able to take part in the study.
- PSA-value must have declined below 0.2 ng/ml prior to randomization
- Adequate hematologic, hepatic, and renal function:
- Hematologic
- Haemoglobin ≥9.0 g/dL independent of transfusions
- Neutrophils ≥1.5 Ths./µL
- Hepatic:
- Total bilirubin ≤1.5X upper limit of normal (ULN) [except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN]
- Alanine (ALT) and aspartate (AST) aminotransferase ≤2.5X ULN
- Renal:
- Serum creatinine <1.5X ULN or calculated creatinine clearance ≥50 mL/min
- Serum potassium ≥3.5 mM
- Serum albumin ≥ 3.0 g/dL.
- Ability to swallow study medication tablets.
- In case of apalutamide treatment: Agrees to use a condom and another highly effective method of birth control if he is having sex with a woman of childbearing potential or to use a condom if he is having sex with a woman who is pregnant
Who cannot join
- Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone q.d.
- Prior cytotoxic chemotherapy or biologic therapy for the treatment of prostate Cancer.
- Prior or current treatment of prostate cancer with apalutamide, enzalutamide, darolutamide, or other investigational agents targeting the androgen receptor.
- Prior therapy with Sipuleucel-T or other vaccination or immunogenic therapy for the treatment of prostate Cancer.
- Prior treatment with abiraterone acetate or other androgen synthesis inhibitors (e. g. ketoconazole, TAK700, TOK001).
- Use of 5-α reductase inhibitors (eg, dutasteride, finasteride) ≤4 weeks prior to randomization.
Show all 29Show fewer
- Prior surgical castration or medical castration using LHRH-Agonists or GnRH-Antagonists.
- Prior or current radiation or radionuclide (including radium-223 dichloride) therapy for treatment of prostate cancer (adjuvant radiation of the prostate bed without involvement of the regional lymph node template as by standard of care in case of positive surgical margins (R1) is allowed).
- Prior or current systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
- Any lymph node or distant metastasis.
- History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
- Current or prior treatment with anti-epileptic medications for the treatment of seizures.
- Management of cardiovascular risk factors, such as hypertension, diabetes or dyslipidaemia should be optimised as per standard of care before treatment with apalutamide will be initiated
- 13.1. Uncontrolled hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg. For patients with relevant comorbidities (e.g. diabetes) systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg). Patients with a history of hypertension are allowed provided that blood pressure is controlled by anti-hypertensive Treatment
- 13.2. Patients with uncontrolled diabetes defined as HbA1c ≥7.5%
- 13.3. Patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl. For patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl and SCORE-value of 1-5%: In case of a SCORE-value of <1% a LDL cholesterol level of up to 115 mg/dl is acceptable. In case of increased LDL cholesterol above these values a statin-therapy can be initiated and a rescreening within 4 weeks is possible
- 13.4. Cardiovascular risk assessment via an appropriate score (e.g. the SCORE-Chart for the European high/low risk score from the European Society of Cardiology) and ≥ borderline risk i.e. 10% of developing cardiovascular events within 10 years without prior established cardiovascular disease
- Active or symptomatic viral hepatitis or chronic liver disease or HIV.
- History of pituitary or adrenal dysfunction.
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline.
- Any condition that requires treatment with digoxin, digitoxin, and other digitalis drugs.
- Long QT-Syndrome.
- Atrial Fibrillation, or other cardiac arrhythmia requiring therapy.
- Other malignancy with a ≥30% probability of recurrence within 24 months, except non-melanoma skin Cancer.
- Any condition, which, in the opinion of the investigator, would preclude participation in this trial.
- Gastrointestinal conditions affecting Absorption.
- Hypersensitivity to the active substance, or to any of the excipients of the study medication.
- Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol.
- Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial. There may be exceptions at the discretion of the (coordinating) investigator.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
Germany17 sites
Universitätsklinikum Augsburg Klinik für Urologie
Augsburg, 86156
GFO Kliniken Rhein-Berg
Bergisch Gladbach, 51465
Urologische Partnerschaft Köln
Cologne, 50968
Urologicum Duisburg
Duisburg, 47169
Universitätsklinikum Düsseldorf
Düsseldorf, 40225
Universitätsklinikum Essen
Essen, 45147
Universitätsklinikum Frankfurt
Frankfurt, 60590
St. Antonius-Hospital Gronau GmbH Klinik für Urologie, Kinderurologie und Urologische Onkologie
Gronau, 48599
Universitätsklinikum Jena
Jena, 07747
KLINIKUM LANDSHUT gemeinnützige GmbH
Landshut, 84034
Klinikum Leverkusen gGmbH, Klinik für Urologie
Leverkusen, 51375
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Lübeck, 23538
Universitätsklinikum Magdeburg
Magdeburg, 39120
University Hospital Münster
Münster, North Rhine-Westfalia, 48149
Klinik für Urologie, Lehrstuhl Regensburg, Am Caritas Krankenhaus St. Josef
Regensburg, 93053
UroGynZentrum
Wuppertal, 42103
Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke
Wuppertal, 42283
Austria4 sites
Medizinische Universität Innsbruck
Innsbruck, 6020
Ordensklinikum Linz GmbH Elisabethinen
Linz, 4020
Uniklinikum Salzburg, Landeskrankenhaus
Salzburg, 5020
Hanusch-Krankenhaus
Vienna, 1140
About this study
Official title: A Randomized, Open-label, Phase 2 Study of Adjuvant Apalutamide or Standard of Care in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy
The primary objective of this trial is to determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE) in comparison to standard of care (SOC).
- Conditions
- Prostatic Neoplasms
- Being tested
- Standard of care, Apalutamide 60Mg Tab
- Keywords
- prostate cancer, apalutamide, radical prostatectomy, randomized, high risk adenocarcinoma, neoplasm
- Medical subject headings
- Prostatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of careOther
- Observation only or
- An optional adjuvant radiation of the prostate bed in case of positive surgical margin
Apalutamide 60Mg TabDrug
(4 x 60 mg) once daily on days 1-28 of a 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Other | 1. Observation only or
2. An optional adjuvant radiation of the prostate bed in case of positive surgical margin Receives: Other: Standard of care |
| Apalutamide | Experimental | 30 cycles apalutamide 240 mg (4 x 60 mg) once daily on days 1-28 of a 28-day cycle in addition to standard of care Receives: Other: Standard of care; Drug: Apalutamide 60Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS).
This endpoint is defined as time interval from randomization until BCR (irrespective of the PSADT), metastases, or death from any cause, whichever occurs first. BCR is defined as a PSA ≥ 0.2 ng/ml that has risen on at least two separate occasions at least four weeks ± 3 days apart and measured by the central PSA-lab. The time of BCR is then backdated to the time of the first increased PSA measurement.
Metastatic disease will be defined as the presence of bone metastases visualized on bone scan prostate cancer working group 3 (PCWG3)-criteria; and/or visceral (e.g. liver, lung, brain) or extra-pelvic nodal metastases visualized on CT scan (or MRI scan) (RECIST 1.1-criteria). Evaluations will be performed every 6 months once BCR occurred or sooner if clinically indicated.
For a patient with none of these events before the end of follow-up, observation of PFS will be censored at the date of his date of last contact.
Measured: From date of randomization until the date of first documented progression (BCR or metastases) or date of death from any cause, whichever came first, assessed up to 7 years"
Secondary outcomes (2)
PSA doubling time (PSADT)
In case of a BCR, PSA kinetics as the PSADT are calculated based on the monthly PSA measurements during the first six months after the BCR. The values used to determine the BCR are included in the calculation of PSA kinetics as well.
PSADT is calculated according to Pound et al. by the natural log of 2 (0.693) divided by the slope of the relationship between the log of PSA and time of PSA measurement (i.e. time from BCR) for each patient [33]. PSADT can also be assessed using the MSKCC PSADT calculator (https://www.mskcc.org/nomograms/prostate/psa_doubling_time) using the above definitions.
Measured: If BCR occurs up to 6 months later
Incidence of Adverse Events [Safety and Tolerability]
Safety and tolerability assessed on the basis of adverse events, more precisely adverse events, serious adverse events, adverse reactions, and serious adverse reactions
Measured: From date the informed consent is signed until BCR occured and PSADT was calculated or when distant metastasis occurred (both with or without BCR) or date of death from any cause, whichever came first, assessed up to 7 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2020
- Study start10 Dec 2020
- Primary completion30 Nov 2028 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität Münster
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Responsible party
- Sponsor
- Investigators
- Martin Bögemann, Univ.-Prof. Dr. med., Principal investigator, Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04295447
- Sponsor's protocol ID
- UKM17_0018
- Acronym
- ADAM
- Status last verified
- Jun 2024
- First submitted
- 20 Feb 2020
- Last updated
- 20 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Phase 2 Study of Adjuvant Apalutamide or Standard of Care in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer After Radical Prostatectomy
- ClinicalTrials.gov ID
- NCT04295447
- Acronym / sponsor ID
- ADAM / UKM17_0018
- Conditions
- Prostatic Neoplasms
- Keywords
- prostate cancer, apalutamide, radical prostatectomy, randomized, high risk adenocarcinoma, neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- Universität MünsterUniversity, hospital or other
- Collaborators
- Janssen Pharmaceutica N.V., Belgium
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 30 Nov 2028 (estimated)
- Study completion
- 30 Nov 2028 (estimated)
- First posted
- 4 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this trial is to determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE) in comparison to standard of care (SOC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Other | Other: Standard of care1. Observation only or 2. An optional adjuvant radiation of the prostate bed in case of positive surgical margin |
| Apalutamide | Experimental | Other: Standard of care, Drug: Apalutamide 60Mg Tab30 cycles apalutamide 240 mg (4 x 60 mg) once daily on days 1-28 of a 28-day cycle in addition to standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Signed informed consent form (ICF).
- Men ≥ 18 years of age.
- Patients with histologically confirmed adenocarcinoma of the prostate after radical prostatectomy.
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.
- Exclusion of metastatic disease by computed tomography (CT)-scan of abdomen (magnetic resonance imaging (MRI) of abdomen is possible) and bone scan prior to study inclusion. A PSMA PET-CT/MRI is possible. In this case it has to be done with a diagnostic CT/MRI with contrast media and not with a low dose CT-scan only. In case PSMA-PET imaging has been done, a bone scan can be omitted. CT/MRI, and bone-scan imaging or PSMA PET-CT/MRI administered ≤12 weeks before RPE may be used for screening.
Key exclusion criteria (29 listed)
- Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone q.d.
- Prior cytotoxic chemotherapy or biologic therapy for the treatment of prostate Cancer.
- Prior or current treatment of prostate cancer with apalutamide, enzalutamide, darolutamide, or other investigational agents targeting the androgen receptor.
- Prior therapy with Sipuleucel-T or other vaccination or immunogenic therapy for the treatment of prostate Cancer.
- Prior treatment with abiraterone acetate or other androgen synthesis inhibitors (e. g. ketoconazole, TAK700, TOK001).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of care1. Observation only or 2. An optional adjuvant radiation of the prostate bed in case of positive surgical margin | Other | Apalutamide, Standard of care |
| Apalutamide 60Mg Tab(4 x 60 mg) once daily on days 1-28 of a 28-day cycle | Drug | Apalutamide |
Primary outcome
Progression-free survival (PFS).
Time frame: From date of randomization until the date of first documented progression (BCR or metastases) or date of death from any cause, whichever came first, assessed up to 7 years"
This endpoint is defined as time interval from randomization until BCR (irrespective of the PSADT), metastases, or death from any cause, whichever occurs first. BCR is defined as a PSA ≥ 0.2 ng/ml that has risen on at least two separate occasions at least four weeks ± 3 days apart and measured by the central PSA-lab. The time of BCR is then backdated to the time of the first increased PSA measurement. Metastatic disease will be defined as the presence of bone metastases visualized on bone scan prostate cancer working group 3 (PCWG3)-criteria; and/or visceral (e.g. liver, lung, brain) or extra-pelvic nodal metastases visualized on CT scan (or MRI scan) (RECIST 1.1-criteria). Evaluations will be performed every 6 months once BCR occurred or sooner if clinically indicated. For a patient with none of these events before the end of follow-up, observation of PFS will be censored at the date of his date of last contact.
2 secondary outcomes
PSA doubling time (PSADT)
Time frame: If BCR occurs up to 6 months later
Incidence of Adverse Events [Safety and Tolerability]
Time frame: From date the informed consent is signed until BCR occured and PSADT was calculated or when distant metastasis occurred (both with or without BCR) or date of death from any cause, whichever came first, assessed up to 7 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
Related trials for Prostatic Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Bögemann, Univ.-Prof. Dr. med. principal investigator
Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apalutamide 60Mg Tab in people with Prostatic Neoplasms, run by Universität Münster at 21 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 21 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany, Austria. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS). (time frame: From date of randomization until the date of first documented progression (BCR or metastases) or date of death from any cause, whichever came first, assessed up to 7 years"). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jun 2024.