Primary Objective: • To determine the clinical Progression Free Survival (cPFS) in our study cohort of patients with mCRPC and 68Ga-PSMA-PET/CT selected bone-only disease (PET-bone only group). The cPFS will be compared to the cPFS of patients with…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical progression free survival (cPFS). cPFS will be defined as the time
from first Radium-223 treatment to the date of confirmed progression: clinical
progression (WHO PS * 3, new prostate cancer symptoms, skeletal related events,
a persisting rise in both PSA and ALP) or radiographic progression based on
ceCT or bone scan; start of subsequent treatment (including External Beam
Radiotherapy: EBRT and radionuclide therapy to treat generalized pain); death
or censored at last follow-up. Whichever comes first. Routine interim imaging
in patients that do not show clinical signs of disease progression will not be
permitted.
Secondary outcome
• Patient reported outcome measures (PROMs). Each participant will be asked to
complete questionnaires on health related quality of life (HRQoL), including
the FACT-P, pain (BPI-SF) and analgesics use after every treatment cycle.
• Overall Survival (OS). OS will be defined as time from first Radium-223
treatment to the date of death, or censored at last follow-up.
• 68Ga-PSMA-PET/CT parameters will be assessed at end of treatment.
68Ga-PSMA-PET/CT will be used to evaluate whether clinical progression was
driven by bone lesions or (new) extraskeletal lesions.
• Genomic biomarkers in ctDNA. We will determine whether homologous
recombination deficiency (HRD) assessment in ctDNA correlates with a favorable
therapy response. We will perform deep whole genome sequencing (WGS) of ctDNA
before and after treatment to determine the clonal evolution of prostate cancer
during Radium-223 therapy.
Background summary
Radium-223 is an established radionuclide therapy for patients with metastatic
castration resistant prostate cancer (mCRPC) and symptomatic bone metastasis.
Patients are eligible for this treatment when they have mCRPC and bone
metastases; limited extraskeletal lesions (local prostate, lymph nodes <3 cm)
on conventional contrast enhanced CT (ceCT) were allowed in the registration
trial(1). Previous research revealed that extraskeletal disease on ceCT and
bone scans correlates with a poor response. Meanwhile, 68Ga-PSMA-PET/CT emerged
as more sensitive imaging strategy that increases the detection of
extraskeletal prostate cancer metastases. It is unclear whether these
extraskeletal lesions harbour any predictive value in the treatment of mCRPC
patients with Radium-223.
.
Study objective
Primary Objective:
• To determine the clinical Progression Free Survival (cPFS) in our study
cohort of patients with mCRPC and 68Ga-PSMA-PET/CT selected bone-only disease
(PET-bone only group). The cPFS will be compared to the cPFS of patients with
on PSMA PET/CT-detected extra-skeletal disease (control group). In addition,
cPFS will be compared to an historical cohort of patients that received
standard of care Radium-223 therapy in the ROTOR registry (retrospective
control group).
Secondary Objectives:
• To determine the impact of Radium-223 treatment on patient reported outcome
measures (PROMs) in the selected bone-only group, as compared to the control
group, and in addition, to the retrospective control cohort (ROTOR).
• To determine the overall survival (OS) in our selected bone-only cohort of
patients in comparison to the control group and to the retrospective control
cohort (ROTOR).
• To determine the correlation between genomic biomarkers (HRD) in ctDNA and
Radium-223 treatment response in the selected bone-only cohort.
• To evaluate whether clinical progression was driven by bone lesions or (new)
extraskeletal lesions. 68Ga-PSMA-PET/CT will be used to assess these lesions.
Study design
We will conduct a prospective clinical study to determine the clinical response
to Radium-223 therapy among patients with mCRPC with bone only disease
according to 68Ga-PSMA-PET/CT scan. We will include patients (n=60) with mCRPC
that are commencing standard-of-care Radium-223 therapy based on results of
ceCT and bone scans. Each patient will undergo an additional 68Ga-PSMA-PET/CT
scan to determine the presence of potential extra-skeletal disease according to
this imaging modality and plasma sampling for ctDNA analysis. The treating
physician*s will be blinded to the 68Ga-PSMA-PET/CT scan result during
treatment. All imaging should be performed in the 8 weeks prior to start of
Radium-223 therapy. Subsequently, all patients will receive a maximum number of
6 cycles of Radium-223 therapy according to current clinical guidelines (Figure
1). From each participant, data will be collected about clinical (skeletal
related events, SREs), biochemical (alkaline phosphatase: ALP, PSA) and
conventional imaging (ceCT, bone scans) response. We will also measure quality
of life (QoL) parameters by serial assessment of PROMs. Upon clinical
progression, the result of the baseline 68Ga-PSMA-PET/CT will be unblinded to
allow monitoring of inclusions in the *PET-bone-only* cohort. All patients will
undergo a second 68Ga-PSMA-PET/CT in addition to routine ceCT- bone scans to
determine the location of the disease progression. The clinical results
obtained with the 68Ga-PSMA-PET/CT selection strategy, will be compared to the
treatment outcomes collected in our previously reported ROTOR registry(3).
Study burden and risks
All patients will receive standard of care Radium-223 treatment. Study
participation will require completion of two 68Ga-PSMA-PET/CT scans (1), a
maximum number of 4 plasma samplings (2x 10 mL Streck tubes) for genomics
analysis (2) and monthly PROM assessments from inclusion until disease
progression (3). Each PROM assessment will consist of either a digital
completion of two questionnaires about quality of life (FACT-P) and pain
(BPI-S) and registration of pain medications. Patients will be exposed to a
total 12 mSv of radiation due to the two additional 68Ga-PSMA-PET/CT scans,
which is a low dose of radiotion relative to Radium-223 radionuclide treatment
to which to patient consented. We therefore consider the risks of these study
procedures negligible. Radium-223 treatment is currently only registered for
the treatment of patients with mCRPC, based on ALSYMPCA inclusion criteria
(i.e. no extra-skeletal disease on ceCT and bone scan). This study can
therefore only be performed among these patients. Patients that will have
extra-skeletal metastases on 68Ga-PSMA PET/CT (control group), will be treated
with Radium-223 according to current clinical guidelines as well, as the
predictive value of having extra-skeletal metastases on PET has not been shown.
We hypothesize that clinical response among these patients will last shorter,
because extra-skeletal metastases will by definition not be treated by
Radium-223.
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
1) Histologically confirmed adenocarcinoma of the prostate.
2) Progressive disease after previous treatment defined as a rise in serum PSA
(PCWG3 criteria(22), see appendix 1) and/or progression on conventional imaging
(PCWG3).
3) A positive bone scan (osteoblastic bone metastases), with at least two
metastases.
4) Hemoglobin concentration >10 g/dl (6.2 mmol/l) and thrombocytes >100 109/l
at baseline.
5) Each patient will need to (continue to) receive adequate bone protective
agents (e.g. bisphosphonates) and androgen deprivation therapy (ADT) according
to current clinical guidelines.
Exclusion criteria
1) ECOG performance score >2
2) Life expectancy < 6 months.
3) Detected extra-skeletal metastases or lymph node metastases (>3 cm short
axis) as identified by conventional imaging (ceCT thorax/abdomen)
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 |
|---|---|
| CCMO | NL86928.041.24 |