1. To evaluate the feasibility of 18F-FDG PET/CT, or WB MRI or both to determine metastatic tumour load before and after treatmentwith Enzalutamide in patients with metastatic prostate cancer.2. To evaluate how these 2 imaging modalities perform…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
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-choline 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 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), P1NP.
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 prostate cancer 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 patients with metastatic prostate cancer.
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 metastatic prostate cancer.
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 with the
addition of Enzalutamide, which has been shown safe and efficacious in large
trials. Also, 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 hormone-sensitive prostate cancer patients with progressive
metastatic disease requiring treatment and who have at least one measurable
metastasis on either PET/CT or WB MRI or both.
Exclusion criteria
Previous androgen deprivation therapy within the last 6 months / Known or
suspected brain metastasis or active leptomeningeal disease / Evidence of
clinically relevant liver/kidney disease/bone marrow failure / history of
seizure or any condition that may predispose to seizure / history of loss of
consciousness or transient ischemic attack within 12 months of enrollment /
Contra-indication for MRI (e.g. pacemaker).
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 | EUCTR2014-001162-10-NL |
| ClinicalTrials.gov | NCT02815033 |
| CCMO | NL52114.058.15 |