Ignite Creation Date:
2024-05-06 @ 11:01 AM
Last Modification Date:
2024-10-26 @ 12:38 PM
Study NCT ID:
NCT03403777
Status:
COMPLETED
Last Update Posted:
2019-03-05
First Post:
2018-01-02
Brief Title:
Avelumab in Refractory Testicular Germ Cell Cancer
Sponsor:
National Cancer Institute Slovakia
Organization:
National Cancer Institute Slovakia
Study Overview
Official Title:
Phase II Study of Avelumab in Multiple RelapsedRefractory Testicular Germ Cell Cancer
Status:
COMPLETED
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a proof-of-concept study to define efficacy of AVELUMAB in patients with multiple relapsedrefractory germ cell tumors GCTs Data suggest that PD-L1 is overexpressed in TGCTs and PD-L1 expression is significantly higher in GCTs in comparison to normal testicular tissuePatients with low PD-L1 expression had significantly better progression-free survival hazard ratio HR 040 95 CI 016 - 101 p 0008 and overall survival HR 043 95 CI 015 - 123 p 0040 compared to patients with high PD-L1 expression These data suggest that PD-1PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1PD-L1 signaling in GCTs
Detailed Description:
Germ-cell tumours GCTs are extraordinarily chemosensitive and resemble the clinical and biological characteristics of a model for the cure of cancer Nonetheless a small proportion of patients do not have a durable complete remission CR with initial chemotherapy Only 20-40 of them will be cured with the use of platinum-containing standard-dose or high-dose salvage chemotherapy with autologous stem cell transplantation ASCT Patients who fail to be cured after second-line salvage therapy have an extremely poor prognosis and long term survival had been documented in 5 Paclitaxel plus ifosfamide and cisplatin is considered as a standard salvage chemotherapy in relapsed good prognosis GCTs however up to 40 of favourable prognosis patients failed to achieve durable response to this combination and therefore new treatment strategies are warranted
Recent data suggest that PD-L1 is overexpressed in TGCTs including 73 seminomas and 64 non-seminomatous tumors but none of normal testicular tissue specimens exhibited PD-L1 expression In previous study that included 140 patients PD-L1 was significantly higher in GCTs in comparison to normal testicular tissue mean QS 529 vs 032 p 00001 Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma teratoma yolk sac tumor and seminoma PD-L1 expression was associated with poor prognostic features including 3 metastatic sites increased serum tumor markers andor non-pulmonary visceral metastases Patients with low PD-L1 expression had significantly better progression-free survival hazard ratio HR 040 95 CI 016 - 101 p 0008 and overall survival HR 043 95 CI 015 - 123 p 0040 compared to patients with high PD-L1 expression Figure 1
These data suggest that PD-1PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1PD-L1 signaling in GCTs and phase II study is warranted
Recent data suggest that PD-L1 is overexpressed in TGCTs including 73 seminomas and 64 non-seminomatous tumors but none of normal testicular tissue specimens exhibited PD-L1 expression In previous study that included 140 patients PD-L1 was significantly higher in GCTs in comparison to normal testicular tissue mean QS 529 vs 032 p 00001 Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma teratoma yolk sac tumor and seminoma PD-L1 expression was associated with poor prognostic features including 3 metastatic sites increased serum tumor markers andor non-pulmonary visceral metastases Patients with low PD-L1 expression had significantly better progression-free survival hazard ratio HR 040 95 CI 016 - 101 p 0008 and overall survival HR 043 95 CI 015 - 123 p 0040 compared to patients with high PD-L1 expression Figure 1
These data suggest that PD-1PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1PD-L1 signaling in GCTs and phase II study is warranted
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None