An Open-label, Single-arm, Rater-blinded, Multicenter Phase 1/2 Study to Assess Safety and Diagnostic Accuracy and Radiotherapeutic Implications of Pre-operative Ga-68-PSMA-11 PET/CT Imaging in Comparison to Histopathology, in Newly-diagnosed Prostate Cancer (PCA) Patients at High Risk for Metastasis, Scheduled for Radical Prostatectomy (RP) With Extended Pelvic Lymph Node Dissection (EPLND)
- Conditions
- High-risk Prostate CancerProstate Cancer MetastaticLymphnode MetastasisC61Malignant neoplasm of prostate
- Registration Number
- DRKS00013701
- Lead Sponsor
- Deutsches Krebsforschungszentrum (DKFZ) Heidelberg
- Brief Summary
In conclusion, efficacy results showed that; • At patient level, Ga-68-PSMA-11 PET/CT imaging detected prostate cancer tissue within the prostate gland with a higher sensitivity and a slightly reduced sensitivity at quadrant level. Specificity of prostate gland could not be calculated at patient level and was low at quadrant level. • Ga-68-PSMA-11-Study sensitivity and specificity assessment based on lymph nodes showed a high specificity and PPV, and a moderate sensitivity. The moderate sensitivity was within the range of published data. o Sensitivity slightly decreased for the gross-region (pelvic left/right) assessment o Low sensitivity for the sub-region assessment was obtained o Exploratory analysis of lymph nodes with a bigger diameter resulted in increased sensitivity • Comparison of Ga-68-PSMA-11 PET/CT imaging and 99mTc bone scintigraphy in detecting bone metastases did not give a clear pattern. • The SUV peak measured in prostate correlated with the Gleason score categories. It may therefore be an indicator of Gleason score but may not reliably predict the exact Gleason score. • Change in clinical management due to RP and EPLND not being conducted was observed in a small fraction of patients. The impact of pre-operative Ga-68-PSMA-11 PET/CT imaging on target volume definition of radiotherapy was also investigated but did not yield clear results. PSMA-guided radiotherapy led to a small reduction (1–2%) of the risk of obstruction/ perforation of the small bowel and late rectal bleeding grade =2 which was not significant. In contrast, there was a higher risk (1–14%) for late effects grade =3 for the bladder compared to conventional treatment plans. • Exploratory analyses of molecular and clinical biomarkers showed that; o Detection rate of CTC was within the expected range. Weak to strong intensity of PSMA expression was also detected in part of the analysed patient samples. o uPAR expression level correlated positively with the age of the patients (i.e uPAR levels increased with age of the patients) and negatively with miR-375 expression. The safety data showed that; • Ga-68-PSMA-11 was safe and well-tolerated in the study population and may be used safely in further studies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Male
- Target Recruitment
- 173
1. Written informed consent.
2. Male = 18 years of age.
3. Histologically confirmed adenocarcinoma of the prostate.
4. High risk for metastasis, defined by either:
a. stadium cT3 according to TNM classification, or
b. Gleason Score >7, or
c. PSA >20 ng/mL.
5. Patient scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (EPLND) according to current guidelines 8 - 42 days after start of study.
6. Consent to practise contraception until end of study (6 days after Ga-68-PSMA-11 injection).
7. Preoperative PCA staging performed according to guidelines, to include pelvic MRI or CT and 99mTc bone scintigraphy, not older than 56 days prior to inclusion, according to standard of care.
1. Known hypersensitivity to Ga-68-PSMA-11 or its components.
2. Presence of known lymph node metastases outside surgical field.
3. More than 5 bone metastases, as determined by 99mTc bone scintigraphy.
4. Previous prostate cancer therapy.
5. Administration of any kind of PET tracer within a period corresponding to 8 half-lives of the respective radionuclide.
6. Any other investigational medicinal product within 30 days prior and 7 days after receiving study medication.
7. Evidence of neuroendocrine small cell carcinoma.
8. Subjects not able to declare meaningful informed consent on their own (e.g. with legal guardian for mental disorders).
9. Simultaneous participation in other clinical trials
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - True positive fraction (TPF) and false positive fraction (FPF) of identified tumour tissue in soft tissue, analysed separately for prostate gland and pelvic lymph nodes, after localization of tumor tissue on the PET/CT scan, using histopathology as standard of truth.; time frame: up to day 42<br>- Frequency of occurrence and severity of abnormal findings in safety investigations (physical examination, vital signs, 12-lead ECG, pulse oximetry, clinical laboratory, adverse events, concomitant medication).; time frame: Day 0 - Day 7
- Secondary Outcome Measures
Name Time Method - Number of identified bone lesions, per patient.; time frame: Day 1<br>- Correlation coefficient of recovery-corrected SUV (standardized uptake value) values plotted against Gleason score in primaries after RP; time frame: Day 1<br>- Percentage of subjects for whom the RP and EPLND will not be conducted; time frame: Day 1<br>- Quantity of circulating tumour cells in blood; time frame: Day 1