Male Urogenital Diseases, mCRPC
Conditions
Keywords
mCRPC, 68Ga-PSMA-PET/CT, Radium-223, Bone only-disease
Brief 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.
Detailed description
Study design: The investigators will conduct a prospective clinical study in which patients with mCRPC and bone-only disease according to ceCT and bone scan will receive standard-of-care treatment with Radium-223. In addition to standard-of-care systemic treatment, each patient will undergo an additional 68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis. The treating physicians will be blinded to the result of the baseline 68Ga-PSMA-PET/CT scan. Each patient will receive a maximum number of 6 cycles of Radium-223 therapy according to current clinical guidelines and will undergo response evaluation by ceCT and bone scans upon clinical progression. At clinical progression, each patient will undergo a second 68Ga-PSMA-PET/CT to determine the location of disease progression and assess the value of 68Ga-PSMA-PET/CT imaging as a response measure. The clinical response of Radium-223 therapy in the patients with bone-only disease according to 68Ga-PSMA-PET/CT scanning, will be compared to the treatment outcomes collected in our previously reported ROTOR registry. Secondary aims are to determine the value of ctDNA as predictive biomarker and the value of 68Ga-PSMA-PET/CT imaging in the response assessment.
Interventions
OTHER68Ga-PSMA-PET/CT scan
68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with online patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis. At clinical progression, each patient will undergo a second 68Ga-PSMA-PET/CT to determine the location of disease progression and assess the value of 68Ga-PSMA-PET/CT imaging as a response measure
Sponsors
Bayer
The Netherlands Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
The treating physicians will be blinded to the result of the baseline 68Ga-PSMA-PET/CT scan
Intervention model description
The investigators will conduct a prospective clinical study in which patients with mCRPC and bone-only disease according to ceCT and bone scan will receive standard-of-care treatment with Radium-223. In addition to standard-of-care systemic treatment, each patient will undergo an additional 68Ga-PSMA-PET/CT scan at baseline and will be followed throughout the treatment with online patient reported outcome measure (PROM) questionnaires (Kaiku application) and blood sampling for circulating tumor DNA (ctDNA) analysis.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the prostate. * Progressive disease after previous treatment defined as a rise in serum (Prostate Specific Antigen) PSA (PCWG3 criteria(22), see appendix 1) and/or progression on conventional imaging (PCWG3). * A positive bone scan (osteoblastic bone metastases), with at least two metastases. * Hemoglobin concentration \>10 g/dl (6.2 mmol/l) and thrombocytes \>100 109/I at baseline. * 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
* Eastern Cooperative Oncology Group (ECOG) performance score \>2 * Life expectancy \< 6 months. * Detected extra-skeletal metastases or lymph node metastases (\>3 cm short axis) as identified by conventional imaging (ceCT thorax/abdomen)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical progression free survival (cPFS) | Up to 28 weeks | The primary study endpoint will be clinical progression free survival (cPFS) in 30 patients with bone-only disease according to PSMA PET/CT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline and changes in 68 Ga-PSMA-PET-CT parameters | Baseline and until progression | Baseline and changes in 68Ga-PSMA-PET/CT parameters (disease localizations, extent of disease, tumor volume). |
| Genomic biomarkers in ctDNA | Before treatment, cycle 3 and 5 and with progression | 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 to determine the clonal evolution of prostate cancer during Radium-223 therapy. |
| Patient reported outcome measures ( PROMs). | In screening and cycle 2,3,4,5,6 (every 4 weeks) and with progression | complete questionnaires on health related quality of life (HRQoL), including the (Functional Assessment of Cancer Therapy) FACT-P: Score 1 to 4, Brief pain Inventory (BPI-SF): scale score from 1 to 10, and analgesics use; name, dosing, frequence and after every treatment cycle. |
| Overall survival (OS) | In Follow up (q6months, max 24 months) | OS will be defined as time from first Radium-223 treatment to the date of death, or censored at last follow-up. |
Countries
Netherlands
Contacts
Primary ContactJ.C. van der Mijn, Dr.
Outcome results
None listed