Prostate Cancer MetastaticPhase 2NCT02814968
PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide
A Phase 2 study testing Enzalutamide, 18-FDG PET/CT and Whole body MRI in people with Prostate Cancer Metastatic, run by The European Uro-Oncology Group at 1 site in Netherlands.
Trial summary
The aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer Metastatic
- What is being tested?
- Enzalutamide, 18-FDG PET/CT and Whole body MRI
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2015to Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Male aged 18 years or older;
- Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
- Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy;
- Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 5 ng/mL but preferably >10 ng/mL;
- Progressive disease as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 18F-FDG PET/CT, Whole Body MRI or both;
- Castrate serum levels of testosterone < 50 ng/dL or < 1.7 nmol/L;
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- Anti-androgen withdrawal for at least 6 weeks for bicalutamide, nilutamide or flutamide for at least 6 weeks;
- No prior treatment with cytotoxic chemotherapy;
- Eastern Cooperative Oncology Group (ECOG) score 0-2;
- A life expectancy of at least 12 months;
- Written informed consent.
Who cannot join
- Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
- Known or suspected brain metastasis or active leptomeningeal disease;
- History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer;
- Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
- Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
- Hemoglobin <6 mmol/L, White blood cells < 4.0 x10^9/L, platelets < 100 x 10^9/L;
- History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrolment (Day 1 visit);
- Contra-indication for MRI (e.g. pacemaker).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Open-label, Single-arm, Efficacy and Imaging Study of Oral Enzalutamide in Chemo-Naïve Patients With Progressive Prostate Cancer Who Have Failed Androgen Deprivation Therapy (Castration-resistant Prostate Cancer Patients)
The aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in castration-resistant prostate cancer patients.
The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide in castration-resistant prostate cancer patients.
In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.
Read the detailed description
Castration-resistant prostate cancer patients eligible for 2nd line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs.
All subjects will undergo 18F-FDG PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.
- Conditions
- Prostate Cancer Metastatic
- Being tested
- Enzalutamide, 18-FDG PET/CT, Whole body MRI, Bone scan
- Keywords
- Castration-resistant prostate cancer, Enzalutamide, Imaging, PET/CT, Whole body MRI, Circulating tumour cells, Cell-free tumour DNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzalutamideDrug
Also called Xtandi
18-FDG PET/CTDevice
Whole body MRIDevice
Bone scanDevice
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Subjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment. Receives: Drug: Enzalutamide; Device: 18-FDG PET/CT; Device: Whole body MRI; Device: Bone scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) at 6 months
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria:
- Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions.
- Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 6 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
Measured: 6 months
Progression-Free Survival (PFS) at 12 months
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria:
- Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions.
- Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 12 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
Measured: 12 months
Secondary outcomes (19)
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
Response as PSA nadir.
Measured: 12 months
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements).
PSA doubling time
Measured: 12 months
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria.
Progression of bone lesions
Measured: 6 and 12 months
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.
Radiological assessment of spinal cord compression or pathological fracture
Measured: 6 and 12 months
Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments
Assessment of external beam radiation therapy to relieve skeletal pain, occurrence of a new symptomatic pathologic bone fracture, spinal cord compression, tumour-related orthopedic surgical intervention or change of anti-neoplastic therapy to treat bone pain
Measured: 12 months
Number of participants with change in CTC measurements correlated to radiological PFS.
Assessment of radiological PFS
Measured: 6 and 12 months
Percent change from baseline in serum concentration of circulating testosterone (T).
Change in circulating testosterone
Measured: 12 months
Percent change from baseline in serum concentration of dihydrotestosterone (DHT).
Change in serum concentration of dihydrotestosterone
Measured: 12 months
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG).
Changes of SHBG
Measured: 12 months
Percent change from baseline in serum concentration of androstenedione (A).
Changes of androstenedione from baseline
Measured: 12 months
Number of participants with changes in biomarkers of bone turnover correlated to PSA.
Changes in biomarkers
Measured: 12 months
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation.
Assessment of AE and SAEs
Measured: 6 and 12 months
Time to symptomatic progression (including death due to prostate cancer).
Time to progression
Measured: 12 months
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation.
Time to chemotherapy or palliative radiation.
Measured: 12 months
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Quality of life assessment
Measured: 6 and 12 months
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D).
Quality of life assessment
Measured: 6 and 12 months
Changes in Karnofsky score
Changes in Karnofsky score
Measured: 6 and 12 months
Changes in visual analogue scale (VAS) for tumour-related pain.
Pain changes from baseline (QoL)
Measured: 6 and 12 months
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan.
Bone mineral density changes
Measured: 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2016 (estimated)
- Study startFeb 2015
- Primary completionJun 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate Cancer MetastaticStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- The European Uro-Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- Centre for Human Drug Research, Netherlands
- Responsible party
- Sponsor
- Investigators
- Susanne Osanto, MD PhD, Study chair, The European Uro-Oncology Group (EUOG)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02814968
- Sponsor's protocol ID
- EudraCT Number 2014-001161-27
- Status last verified
- Feb 2021
- First submitted
- 18 Jun 2016
- Last updated
- 14 Apr 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-label, Single-arm, Efficacy and Imaging Study of Oral Enzalutamide in Chemo-Naïve Patients With Progressive Prostate Cancer Who Have Failed Androgen Deprivation Therapy (Castration-resistant Prostate Cancer Patients)
- ClinicalTrials.gov ID
- NCT02814968
- Acronym / sponsor ID
- EudraCT Number 2014-001161-27
- Conditions
- Prostate Cancer Metastatic
- Keywords
- Castration-resistant prostate cancer, Enzalutamide, Imaging, PET/CT, Whole body MRI, Circulating tumour cells, Cell-free tumour DNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- The European Uro-Oncology GroupUniversity, hospital or other
- Collaborators
- Centre for Human Drug Research, Netherlands
- Study start
- Feb 2015
- Primary completion
- Jun 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 28 Jun 2016 (estimated)
- 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 aim of the study is to assess the clinical utility of 18F-fluoro-deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) and Whole Body Magnetic Resonance Imaging (MRI) versus conventional bone scan and prostate-specific antigen (PSA) measurements in response prediction to treatment with Enzalutamide in castration-resistant prostate cancer patients.
The study will assess how these 2 imaging modalities perform compared to traditional serial PSA measurements and bone scan in assessing metastatic tumour load, progressive disease and response to treatment with Enzalutamide in castration-resistant prostate cancer patients.
In addition measurements of serially collected circulating tumour cell (CTC) samples, cell-free tumour DNA and RNA will be performed in order to evaluate their predictive value in terms of response measurement.
Detailed description
Castration-resistant prostate cancer patients eligible for 2nd line hormonal treatment will undergo treatment with Enzalutamide (XTANDI). Subjects will receive 1dd 160 mg Enzalutamide orally continuously until progressive disease occurs.
All subjects will undergo 18F-FDG PET/CT scans at baseline, 2 weeks, 2 and 6, 9 and 12 months after starting androgen receptor-directed treatment. All subjects will undergo Whole Body MRI at baseline, 6, 9 and 12 months. Bone scans will be performed at baseline, 3 months, 6 and 12 months. PSA will be measured at baseline and every 4 weeks thereafter until at 12 months. CTC counts and characteristics will be measured at baseline and during Enzalutamide treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Enzalutamide, Device: 18-FDG PET/CT, Device: Whole body MRI, Device: Bone scanSubjects will receive 1 dd 160 mg Enzalutamide orally continuously until progressive disease occurs. Serial PSA measurements, PET/CT scans, Whole Body MRI, bone scans will be performed to assess metastatic tumour load, progressive disease and response to treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male aged 18 years or older;
- Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
- Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy;
- Three consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with PSA of at least > 5 ng/mL but preferably >10 ng/mL;
- Progressive disease as defined by rising PSA levels plus by evidence of progressive and measurable soft tissue or bone disease by 18F-FDG PET/CT, Whole Body MRI or both;
Key exclusion criteria (8 listed)
- Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrolment;
- Known or suspected brain metastasis or active leptomeningeal disease;
- History of another malignancy within the previous 5 years other than curatively treated non melanomatous skin cancer;
- Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of normal at the Screening visit;
- Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit;
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 |
|---|---|---|
| EnzalutamideAlso: Xtandi | Drug | Single arm |
| 18-FDG PET/CT | Device | Single arm |
| Whole body MRI | Device | Single arm |
| Bone scan | Device | Single arm |
Primary outcome
Progression-Free Survival (PFS) at 6 months
Time frame: 6 months
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria: * Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions. * Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 6 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
Progression-Free Survival (PFS) at 12 months
Time frame: 12 months
Defined as the time from the date of randomization to the date of radiological progression or death (patients will be followed beyond the fixed time point of 12 months for continued response cq recurrence, but 12 month is the last fixed primary endpoint assessment). Radiological progression is defined by any of the following criteria: * Soft tissue lesions: Progressive disease on 18F-FDG PET/CT or MRI by RECIST 1.1. Bone or bone marrow lesions: Progressive disease on PET/CT or MRI as evidenced by new lesions or an increase in size of 25% of the sum of target lesions. * Conversion of the 18F-FDG PET signal of the metastases at 2 weeks, 2 or 6 months compared to baseline PET which by comparing it to PFS at 6 and 12 months may be an indicator or drug response. Radiological PFS at 12 months will be compared to a) PET signal conversion and to b) PSA measurements, and changes in number of lesions on the bone scan (conventional work up).
19 secondary outcomes
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
Time frame: 12 months
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements).
Time frame: 12 months
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria.
Time frame: 6 and 12 months
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.
Time frame: 6 and 12 months
Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments
Time frame: 12 months
Number of participants with change in CTC measurements correlated to radiological PFS.
Time frame: 6 and 12 months
Percent change from baseline in serum concentration of circulating testosterone (T).
Time frame: 12 months
Percent change from baseline in serum concentration of dihydrotestosterone (DHT).
Time frame: 12 months
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG).
Time frame: 12 months
Percent change from baseline in serum concentration of androstenedione (A).
Time frame: 12 months
Number of participants with changes in biomarkers of bone turnover correlated to PSA.
Time frame: 12 months
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation.
Time frame: 6 and 12 months
Time to symptomatic progression (including death due to prostate cancer).
Time frame: 12 months
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation.
Time frame: 12 months
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Time frame: 6 and 12 months
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D).
Time frame: 6 and 12 months
Changes in Karnofsky score
Time frame: 6 and 12 months
Changes in visual analogue scale (VAS) for tumour-related pain.
Time frame: 6 and 12 months
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan.
Time frame: 6 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- The European Uro-Oncology GroupLink provided by the sponsor.
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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.
Susanne Osanto, MD PhD study chair
The European Uro-Oncology Group (EUOG)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enzalutamide, 18-FDG PET/CT and Whole body MRI in people with Prostate Cancer Metastatic, run by The European Uro-Oncology Group at 1 site in Netherlands.
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 11 inclusion and 8 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: finished, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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) at 6 months (time frame: 6 months). The study lists 2 primary outcomes in all. 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 14 Apr 2022.