Back to resultsPET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide
Primary Purpose
Prostate Cancer Metastatic
Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Enzalutamide
18-FDG PET/CT
Whole body MRI
Bone scan
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer Metastatic focused on measuring Castration-resistant prostate cancer, Enzalutamide, Imaging, PET/CT, Whole body MRI, Circulating tumour cells, Cell-free tumour DNA
Eligibility Criteria
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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).
Sites / Locations
- Leiden University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
Response as PSA nadir.
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements).
PSA doubling time
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria.
Progression of bone lesions
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.
Radiological assessment of spinal cord compression or pathological fracture
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
Number of participants with change in CTC measurements correlated to radiological PFS.
Assessment of radiological PFS
Percent change from baseline in serum concentration of circulating testosterone (T).
Change in circulating testosterone
Percent change from baseline in serum concentration of dihydrotestosterone (DHT).
Change in serum concentration of dihydrotestosterone
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG).
Changes of SHBG
Percent change from baseline in serum concentration of androstenedione (A).
Changes of androstenedione from baseline
Number of participants with changes in biomarkers of bone turnover correlated to PSA.
Changes in biomarkers
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation.
Assessment of AE and SAEs
Time to symptomatic progression (including death due to prostate cancer).
Time to progression
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation.
Time to chemotherapy or palliative radiation.
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Quality of life assessment
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D).
Quality of life assessment
Changes in Karnofsky score
Changes in Karnofsky score
Changes in visual analogue scale (VAS) for tumour-related pain.
Pain changes from baseline (QoL)
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan.
Bone mineral density changes
Full Information
NCT ID
NCT02814968
First Posted
June 18, 2016
Last Updated
April 6, 2022
Sponsor
The European Uro-Oncology Group
Collaborators
Centre for Human Drug Research, Netherlands
1. Study Identification
Unique Protocol Identification Number
NCT02814968
Brief Title
PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide
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)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
June 2020 (Actual)
Study Completion Date
December 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The European Uro-Oncology Group
Collaborators
Centre for Human Drug Research, Netherlands
4. Oversight
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer Metastatic
Keywords
Castration-resistant prostate cancer, Enzalutamide, Imaging, PET/CT, Whole body MRI, Circulating tumour cells, Cell-free tumour DNA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
Xtandi
Intervention Type
Device
Intervention Name(s)
18-FDG PET/CT
Intervention Type
Device
Intervention Name(s)
Whole body MRI
Intervention Type
Device
Intervention Name(s)
Bone scan
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) at 6 months
Description
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).
Time Frame
6 months
Title
Progression-Free Survival (PFS) at 12 months
Description
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).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
Description
Response as PSA nadir.
Time Frame
12 months
Title
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA measurements).
Description
PSA doubling time
Time Frame
12 months
Title
Progression of bone lesions detected with bone scan according to Prostate Cancer Working Group 2 (PCWG2) criteria.
Description
Progression of bone lesions
Time Frame
6 and 12 months
Title
Radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.
Description
Radiological assessment of spinal cord compression or pathological fracture
Time Frame
6 and 12 months
Title
Occurrence of Symptomatic Skeletal Events (SSE) evaluated by combination of clinical and radiological assessments
Description
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
Time Frame
12 months
Title
Number of participants with change in CTC measurements correlated to radiological PFS.
Description
Assessment of radiological PFS
Time Frame
6 and 12 months
Title
Percent change from baseline in serum concentration of circulating testosterone (T).
Description
Change in circulating testosterone
Time Frame
12 months
Title
Percent change from baseline in serum concentration of dihydrotestosterone (DHT).
Description
Change in serum concentration of dihydrotestosterone
Time Frame
12 months
Title
Percent change from baseline in serum concentration of sex hormone binding globulin (SHBG).
Description
Changes of SHBG
Time Frame
12 months
Title
Percent change from baseline in serum concentration of androstenedione (A).
Description
Changes of androstenedione from baseline
Time Frame
12 months
Title
Number of participants with changes in biomarkers of bone turnover correlated to PSA.
Description
Changes in biomarkers
Time Frame
12 months
Title
Number of participants with adverse events (AEs) and serious adverse events (SAEs) leading to treatment discontinuation.
Description
Assessment of AE and SAEs
Time Frame
6 and 12 months
Title
Time to symptomatic progression (including death due to prostate cancer).
Description
Time to progression
Time Frame
12 months
Title
Time to initiation of salvage systemic therapy, including chemotherapy, or palliative radiation.
Description
Time to chemotherapy or palliative radiation.
Time Frame
12 months
Title
Quality of life measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
Description
Quality of life assessment
Time Frame
6 and 12 months
Title
Quality of life measured by the EuroQol 5-Dimension QoL Instrument (EQ-5D).
Description
Quality of life assessment
Time Frame
6 and 12 months
Title
Changes in Karnofsky score
Description
Changes in Karnofsky score
Time Frame
6 and 12 months
Title
Changes in visual analogue scale (VAS) for tumour-related pain.
Description
Pain changes from baseline (QoL)
Time Frame
6 and 12 months
Title
Changes in bone mineral density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA) scan.
Description
Bone mineral density changes
Time Frame
6 and 12 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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;
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.
Exclusion Criteria:
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Osanto, MD PhD
Organizational Affiliation
The European Uro-Oncology Group (EUOG)
Official's Role
Study Chair
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
12. IPD Sharing Statement
Links:
URL
http://euog.org/
Description
The European Uro-Oncology Group
Learn more about this trial
PET/CT and WB MRI for Staging and Response in CRPC Patients Receiving Enzalutamide
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