1. To evaluate the feasibility of 18F-FDG PET/CT, or WB MRI or both to determine metastatic tumour load before and after treatment with Enzalutamide in CRPC patients. 2. To evaluate how these 2 imaging modalities perform compared to traditional…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression-Free Survival (PFS) at 6 and 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*s 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 and 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
Biochemical (PSA) response defined as prostate-specific antigen (PSA) nadir.
PSA progression. PSA kinetics measured by PSA doubling time (regular PSA
measurements).
Progression of bone lesions detected with bone scan according to Prostate
Cancer Working Group 2 (PCWG2) criteria. Radiologically confirmed spinal cord
compression or pathological fracture due to malignant progression. A
Symptomatic Skeletal Event (SSE) is defined as external beam radiation therapy
(EBRT) to relieve skeletal pain, new symptomatic pathologic bone fracture,
occurrence of spinal cord compression or tumour-related orthopedic surgical
intervention, or change of anti-neoplastic therapy to treat bone pain.
CTC measurements and comparison with radiological PFS at 6 and 12 months.
Circulating testosterone (T), dihydrotestosterone (DHT), sex hormone binding
globulin (SHBG), androstenedione, DHEA, luteinizing hormone (LH), follicle
stimulating hormone (FSH), prolactin and estradiol assessed as temporal changes
of absolute values and temporal percentage changes of baseline values.
Biomarker assessment / correlative: (next to PSA) biomarkers of bone turnover,
Alkaline Phosphatase, PTH, Ca, Phosphate, 25 (OH)Vitamin D, beta-CTX
(beta-crosslaps), PN1P.
The safety of Enzalutamide as assessed by serious adverse events (SAEs),
severity of adverse events (AEs) graded by National Cancer Institute*s Common
Terminology Criteria for Adverse Events (NCI-CTCAE), discontinuation due to
AEs, as well as new clinically significant changes in physical exam findings,
vital signs, laboratory values, and ECGs.
Time to symptomatic progression (including death due to prostate cancer)
Time to first radiological or symptomatic progression
Time to initiation of salvage systemic therapy, including chemotherapy, or
palliative radiation
Quality of life measured by the Functional Assessment of Cancer
Therapy-Prostate (FACT-P) questionnaire and by the EuroQol 5-Dimension QoL
Instrument (EQ-5D)
Changes in Karnofsky score/ECOG score
Changes in visual analogue scale (VAS) for tumour-related pain
Changes in BMD as measured by DXA scan
Background summary
The detection of tumour deposits/metastatic sites in metastatic prostate cancer
is notoriously difficult and the conventionally used PSA (reflecting tumour
mass and differentiation grade of prostate cancer cells scored as Gleason score
in primary tumours) and bone scintigraphy do not provide accurate information
with regard to responses to treatment. There is an unmet need for robust and
reproducible imaging technology allowing accurate quantification and
qualification of bone plus soft tissue metastases and which are useful to early
predict responses and early detect progressive disease cq. heterogeneity in
tumour responses to novel agents. Importantly, emerging imaging modalities such
as PET/CT or WB MRI theoretically offer advantage over traditional PSA
measurements plus bone scan, but this has never been established in a
prospective study. Therefore, we aim to perform an exploratory study in which
both modalities will be evaluated and compared head-to-head.
Clinical practice is hampered by the poor methods and criteria to assess
progression with the risk of prematurely discontinuing effective therapy in
patients with metastatic castrate resistant prostate cancer (mCRPC) because of
apparent initial progression on bone scan. Ineffective treatment may be stopped
earlier if we have methodology to accurately predict favourable or lack of
favourable responses, whereas early prediction of favourable responses will
allow better patient selection and true patient-tailored treatment. This will
be an asset for drug development programmes and result in decreased costs.
Study objective
1. To evaluate the feasibility of 18F-FDG PET/CT, or WB MRI or both to
determine metastatic tumour load before and after treatment with Enzalutamide
in CRPC patients.
2. To evaluate 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 in CRPC patients.
Study design
Prospective Open-label Observational Cohort Study
Intervention
Oral Enzalutamide
Study burden and risks
The study will be performed mainly using routine treatment practice. However,
the patients will be requested to undergo more imaging sessions which are
basically non-invasive and virtually without risk.
Albinusdreef 2 na
Leiden 2333 ZA
NL
Albinusdreef 2 na
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Adult metastatic prostate cancer patients who are progressive on first-line ADT for metastatic disease and who have at least one measurable metastasis on either 18F-FDG PET/CT or WB MRI or both.
Exclusion criteria
Previous chemotherapy, impaired liver/kidney/bone marrow function, susceptibility for seizures
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001161-27-NL |
| ClinicalTrials.gov | NCT02814968 |
| CCMO | NL52067.058.15 |