Primary objective: to explore 18F-FDHT PET/CT as a predictor of response in patients with metastasized CRPC to be treated with enzalutamide. Secondary objective: to explore 18F-FDHT PET/CT as a predictor of clinical survival endpoints in patients…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary end points:
• Measurements at baseline: SUVmax per lesion, SUVmean per lesion and
SUVmaxavg per scan.
• Measurements after 4 weeks of treatment (study week 5): SUVmax per lesion,
SUVmean per lesion and SUVmaxavg per scan.
• Delta: the difference between SUVmaxavg, SUVmax per lesion and SUVmean per
lesion after 4 weeks of treatment (study week 5)) and SUVmaxavg, SUVmax per
lesion and SUVmean per lesion at baseline (study week 1).
Response is defined as not progressive. Progressive according to Prostate
Cancer Clinical Trials Working Group3:
- For patients with PSA declines at week 13, PSA progression is defined as >=
25% and an absolute increase of >= 2 ng/ml above the nadir (lowest PSA level
after treatment) , which is confirmed by a second value 3 or more weeks later
(i.e. a confirmed rising trend).
-For patients with no PSA decline at week 13, PSA progression is defined as >=
25% increase and an absolute increase of >= 2 ng/ml above baseline PSA.
Secondary outcome
Secondary end points:
• Time of start of enzalutamide to initiation of radiation therapy (including
external beam radiation therapy or systemic radionuclides e.g. Samarium or
Strontium).
• Time of start of enzalutamide to first skeletal-related event (defined as
pathological fracture, spinal cord compression, bone pain requiring palliative
radiotherapy and orthopedic surgery).
• Time of start of enzalutamide to initiation of cytotoxic chemotherapy or
CYP-17 inhibitor (abiraterone).
• Overall survival (defined as the time of start of enzalutamide to date of
death from prostate cancer and death from other cause).
Background summary
Worldwide prostate cancer is the second most frequently diagnosed cancer in
men. While localized prostate cancer can be treated with curative intent,
metastasized prostate cancer has palliative treatment options only. Endocrine
deprivation therapy is the mainstay of treatment for patients with metastasized
prostate cancer. In the end, prostate cancer progresses in the majority of
patients because of progressive tumor growth despite endocrine deprivation
therapy: castration-resistant prostate cancer (CRPC). As CRPC progresses,
approximately 90% of patients will develop bone metastases, in contrast to
lymph node metastases which develop in 20% to 25% of patients. The
determination of response to treatment in patients with CRPC is predominantly
plagued by the presence of non-measurable bone metastases. Furthermore, current
response monitoring of lymph node metastases has several drawbacks. Positron
Emission Tomography (PET) is emerging as a promising imaging modality to
evaluate treatment options and predict therapeutic response timely, objectively
and quantitatively. 16β-[18F]-fluoro-5α-dihydrotestosterone (18F-FDHT) images
the androgen receptor with high binding affinity and selectivity. It is
expected that 18F-FDHTPET/CT can give an indication of success or failure early
in the treatment course as part of clinical management or within the context of
clinical trials. Timely response management may adjust the duration of
individual treatment according to its success.
Study objective
Primary objective: to explore 18F-FDHT PET/CT as a predictor of response in
patients with metastasized CRPC to be treated with enzalutamide.
Secondary objective: to explore 18F-FDHT PET/CT as a predictor of clinical
survival endpoints in patients with metastasized CRPC to be treated with
enzalutamide.
Tertiary objective is to collect biopsies of prostate cancer bone and/or lymph
node metastases, blood and urine specimens for future research.
Study design
18F-FDHTPET/CT scans will be performed at baseline and after 4 weeks of
enzalutamide treatment (study week 5). Response will be determined after 12
weeks of treatment (study week 13) according to Prostate Cancer Clinical Trials
Working Group. Clinical survival endpoints will be collected up to 5 years
after inclusion. Patients need to sign an additional informed consent for
biorepository. Patients can participate in the current study without
participation in biorepository. Biopsies of prostate cancer bone and/or lymph
node metastases, blood (excluding Circulating Tumor Cells) and urine will be
collected at baseline and after 12 weeks of enzalutamide treatment (study week
13). Blood for CTC will be collected at baseline, after 4 weeks of enzalutamide
treatment (study week 5) and after 12 weeks of treatment (study week 13).
Intervention
Ezalutamide 160 mg/day.
Study burden and risks
Burden and risks:
- Study visits: frequency is dependent on the duration of enzalutamide
treatment.
- Venepucture: minimally invasive procedure. Known risks are: infection and
hematoma, frequency is dependent on the duration of enzalutamide treatment.
- Brief Pain Inventory: questionnaire, takes about 10 minutes, once.
- MUGA scan or echocardiogram: echocardiogram: no risks. MUGA scan: an
indwelling intravenous catheter needs to be placed which is a minimally
invasive procedure; risks are infection and hematoma. Radiation burden is
around 3.5 mSv. One of these investigations need to be performed in case of
NYHA class III or IV, once.
- Vital signs (pulse rate and blood pressure will be recorded by automatic
device and temperature by ear monitor): no risks, frequency is dependent on the
duration of enzalutamide treatment.
- Electrocardiogram: no risks, frequency is dependent on the duration of
enzalutamide treatment.
- Physical examination: no risks, frequency is dependent on the duration of
enzalutamide treatment.
- Weight and height: no risks, frequency is dependent on the duration of
enzalutamide treatment.
- Urine collection by patient: no risks, frequency is dependent on the duration
of enzalutamide treatment. A digital rectal examination will be performed
immediately prior to the collection of urine: no risks (only in case of
biorepository): no risks.
- Placement of an indwelling intravenous catheter (18F-FDHT PET/CT scan):
minimally invasive procedure. Known risks are: infection and hematoma, twice.
- Placement of a transurethral catheter (18F-FDHT PET/CT scan): minimally
invasive procedure. This is a routine procedure on the Department of Urology.
Improper catheterization can lead to urethral damage or a urinary tract
infection. These complications are however uncommon. Twice.
- 18F-FDHT PET/CT scan: known risks: to date, other than infrequent transient
intravenous site discomfort and transient taste disturbances, no adverse events
have been noted in clinical 18F-FDHT PET studies. Total 18F-FDHT PET/CT
radiation burden is 5.5 mSv. Furthermore the patient has to lay still on his
back for 30 minutes.Twice.
- US or CT guided biopsy: minimally invasive procedure and minimal risks like
infection and hematoma. Pain will be minimal due to use of local anesthesia. US
guided biopsy is only available for lymph node metastases. CT will give
radiation burden of approximately 3 mSv. Twice. Only in case of participation
in biorepository.
- Enzalutamide: at a daily dose of 160 mg the following treatment-emergent
adverse events were reported at a 5% or greater in the integrated safety
population with >= 2% absolute increase in indicence over the placebo group of
CRPC2: fatigue, arthralgia, diarrhea, hot flush, peripheral edema,
musculoskeletal pain, headache, muscular weakness, insomnia, hematuria,
hypertension and pollakiuria. Other treatment-emergent adverse events reported
in fewer than 5% of patients, but that may be associated with enzalutamide
treatment include: falls, nonpathologic fracture, dry skin, puritus, cognitive
effects and hallucination.
Benefit:
- Results of phase 1 and 2 clinical trials reported that enzalutamide has
significant antitumor
activity (including decreases in PSA, responses in soft tissue, stabilized bone
disease and conversion from unfavorable to favorable circulating tumor cell
counts) in men with chemotherapy-naïve and chemotherapy-treated CRPC.
- The determination of response to treatment in patients with CRPC is
predominantly plagued by the presence of non-measurable bone metastases.
Furthermore, current response monitoring of lymph node metastases has several
drawbacks. It is important that accurate methods are available to monitor CRPC
treatment response, since demands on health care resources are great.18F-FDHT
PET/CT can be a promising imaging modality to evaluate treatment options and
therapeutic response timely, objectively and quantitatively. It is expected
that 18F-FDHT PET/CT can give an indication of success or failure early in the
treatment course as part of clinical management or within the context of
clinical trials. Timely response management may adjust the duration of
individual treatment according to its success.
- Prostate cancer bone and lymph node metastases are seldom available for
experiments. Biopsy material, blood and urine collected in the current trial
will be stored in the PCMM biobank for future experiments.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. Age 50 or older.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
3. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or bilateral orchidectomy.
4. Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bone disease.
5. Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT
6. No prior cytotoxic chemotherapy for prostate cancer.
7. Asymptomatic or mildly symptomatic from prostate cancer
8. Written informed consent
Exclusion criteria
1. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment.
2. Known or suspected brain metastasis or active leptomeningeal disease.
3. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| Other | 4086 |
| EudraCT | EUCTR2012-005431-86-NL |
| CCMO | NL42842.042.13 |