The primary objectives of the Radium223Insight study are: 1. To identify biomarkers for early identification of clinical benefit from radium-223 treatment in mCRPC patients. 2. To better understand immune response during radium-223 treatment in…
ID
Source
Brief title
Condition
- Reproductive and genitourinary neoplasms gender unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Exploratory analysis of multiple biomarkers in relation to failure-free
survival, defined as time to next line of treatment, best supportive care or
death. Next line of treatment or best supportive care will be started upon
clinical, biochemical and/or radiological signs of progression according to the
PCWG3 criteria.
Biomarkers:
a) Blood based biomarkers:
- Conventional markers: tALP decline from baseline to week 12 (confirmed > 3
weeks from week 12) correlates with an increased failure-free survival, and
other endpoints.
- CTC*s: <5 CTC*s/7.5 ml at baseline correlates with an increased failure-free
survival, and other endpoints.
- ctDNA: >50% decline in the allelic fraction of mutant tumor-derived DNA
within total cell-free DNA during treatment correlates with an increased
failure-free survival, and other endpoints.
- Immune profiling data
b) Imaging based biomarkers:
- Bone scintigraphy: 2+2 rule correlates with a decreased failure-free
survival, and other endpoints.
- [68Ga]PSMA PET-CT: Reduction in SUVmax of >30% in the hottest baseline lesion
correlates with an increased failure-free survival, and other endpoints.
- [89Zr]atezolizumab PET-CT
2. Exploratory analysis of the immune response during radium-223 treatment in
relation to failure-free survival as defined above:
- Blood based analysis of immune cells and markers: Calculation of absolute
numbers of immune cells by multi-color flowcytometry, and other endpoints.
- In vivo monitoring of PD-L1 signaling by [89Zr]atezolizumab PET-CT: Analysis
of SUVmax on [89Zr]atezolizumab PET-CT over time, and other endpoints.
- In situ multiplex immune fluorescence of FFPE using automated quantitative
pathology imaging: Quantification of PD-L1 positive tumor cells and immune
cells in biopsy tissue, and other endpoints.
Secondary outcome
1. Characterization of the mutational and immunological profile of
pre-treatment tumor genome in relation to failure free survival as defined
above.
2. Overall survival
3. Skeletal related events
Background summary
Based on the survival results of a randomized phase 3 trial, the European
Medicines Agency (EMA) and Committee for the Assessment of Oncological
Medicines (*Commissie BOM*) have approved radium-223 for the treatment of
metastatic castration resistant prostate cancer (mCRPC) with bone metastases
only. As traditional parameters, including PSA, fail in (early) response
evaluation, other parameters are needed to guide treatment planning in mCRPC
patients. As the efficacy of immunotherapy is limited in mCRPC and radium-223
may initiate an immune response by activation of CD8 T lymphocytes, further
understanding is required for the rational development of combination
strategies, including those with radium-223.
Study objective
The primary objectives of the Radium223Insight study are:
1. To identify biomarkers for early identification of clinical benefit from
radium-223 treatment in mCRPC patients.
2. To better understand immune response during radium-223 treatment in mCRPC
patients.
The secondary objective of the Radium223Insight study is:
1. To characterize the mutational and immunological profile of pre-treatment
tumor genomes of mCRPC patients in relation to clinical benefit.
Study design
This is a prospective, translational, multicenter, hypothesis-generating study
with an exploratory design.
Study burden and risks
Participation in this study requires additional blood draws, imaging and a
pre-treatment bone biopsy.
Total needed blood volume varies between 30-80 ml per blood draw (including
standard laboratory examinations). Blood draws will take place before each
cycle (every four weeks), during follow-up and upon progression in combination
with regular blood draws. Additionally, a limited amount of blood will be drawn
for technical aspects of the PET-CTs. The risk of this limited amount of blood
being drawn is minimal.
In addition, patients will undergo four imaging modalities during treatment:
three bone scintigraphies, three CT scans of the thorax and abdomen, a
CT-guided bone biopsy, three [68Ga]PSMA PET-CT scans and two [89Zr]atezolizumab
PET-CT scans. The bone scintigraphy and the CT-thorax/abdomen at baseline and
at the end of treatment are standard of care. The remaining scans will give an
additional radiation burden of approximately 80 mSv, divided over 24 weeks.
This is about 3% of the estimated effective dose of the radium-223 treatment.
During follow-up CT scans and bone scintigraphies will be performed according
to standard of care. Upon progression an additional [68Ga]PSMA PET-CT will be
performed, which accounts for 6 mSv. The median survival of this patient
population is approximately 24 months. Considering this prognosis and the
relative small additional radiation burden on top of the standard radium-223
treatment, the radiation burden of the imaging protocol is considered justified.
The risk on bleeding or infection during the bone biopsy is considered low.
However, the biopsy can be painful. All safety measures and procedures will be
performed according to local guidelines.
Dr.Molewaterplein 40
Rotterdam 3015 GD
NL
Dr.Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- Histologically confirmed, progressive prostate cancer during ADT.
- Prior treatment with at least two other approved agents for metastatic
prostate cancer, unless the patient can*t or doesn*t want to receive other
treatments.
- Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.
- Life expectancy of 6 months or longer
- Adequate hematologic, renal, and liver function.
Exclusion criteria
- Prior chemotherapy, other than docetaxel.
- Previous hemibody external radiotherapy or systemic radiotherapy with
radioisotopes within the previous 24 weeks.
- A blood transfusion or use of erythropoietin-stimulating agents within the
previous 4 weeks
- Pathological lymphadenopathy > 1.5 cm in the short-axis diameter on CT or
MRI. [68Ga]PSMA positive lymph nodes at baseline are allowed.
- A history of presence of visceral metastases on CT or MRI. Patients with
[68Ga]PSMA positive lesions that are highly suspected for visceral metastases
and are retrospectively visible on CT or MRI should be excluded as well.
- Imminent or established spinal cord compression on CT or MRI.
- A second active malignancy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL66323.078.18 |
| OMON | NL-OMON26890 |