Avelumab in Refractory Testicular Germ Cell Cancer.
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|ClinicalTrials.gov Identifier: NCT03403777|
Recruitment Status : Recruiting
First Posted : January 19, 2018
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Testicular Neoplasms Neoplasms, Germ Cell and Embryonal Neoplasms Testicular Diseases Gonadal Disorders Antineoplastic Agents Molecular Mechanisms of Pharmacological Action||Drug: Avelumab||Phase 2|
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 = 5.29 vs. 0.32, p < 0.0001). 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 and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival (hazard ratio [HR] = 0.40, 95% CI (0.16 - 1.01, p = 0.008) and overall survival (HR = 0.43, 95% CI (0.15 - 1.23, p = 0.040) compared to patients with high PD-L1 expression (Figure 1).
These data suggest that PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs and that there is strong rationale to inhibit PD-1/PD-L1 signaling in GCTs and phase II study is warranted.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Non-randomized, open-label, multi-centre trial to assess efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with refractory germ cell tumors (GCTs). The Simon optimal 2-stage design (see statistical section) will be used. See section 6 (Statistical Considerations) for specific details.|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Avelumab in Multiple Relapsed/Refractory Testicular Germ Cell Cancer.|
|Actual Study Start Date :||November 15, 2017|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||December 31, 2020|
AVELUMAB will be administered intravenously 10mg/kg every 2 weeks. Courses will be repeated every 14 days until progression or unacceptable toxicity. AVELUMAB will be administered as a 1-hour (-10 minutes / +20 minutes, i.e., 50-80 minutes) intravenous (i.v.) infusion. The dose of AVELUMAB will be calculated based on the weight of the subject determined on the day prior to or the day of each drug administration.
AVELUMAB will be administered intravenously 10mg/kg every 2 weeks.
Other Name: Bavencio
- To determine the efficacy (as measured by 12-week progression-free survival) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [ Time Frame: 12-weeks ]12-week progression-free survival
- To describe the favorable response rate of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [ Time Frame: 4-weeks ]Favorable response rate - complete remission and/or partial remission with negative serum tumor markers
- Progression-free survival (PFS) of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [ Time Frame: 12-months ]Progression-free survival (PFS) will be calculated from the beginning of the treatment until progression or death from disease-specific cause on intention-to-treat basis.
- Toxic effects of AVELUMAB in patients with multiple relapsed/refractory germ cell tumors (GCTs). [ Time Frame: 12-weeks ]Toxicity according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03403777
|Contact: Daniela Světlovska, PhD||+421-2-59378 ext firstname.lastname@example.org|
|Contact: Michal Mego, prof||+421-2-59378 ext email@example.com|
|National Cancer Institute||Recruiting|
|Bratislava, Slovakia, 83310|
|Contact: Michal Mego, Prof +421259378 ext 366 firstname.lastname@example.org|
|Contact: Jozef Mardiak, Prof +421259378 ext 108 email@example.com|
|Principal Investigator: Jozef Mardiak, Prof|
|Principal Investigator: Michal Mego, Prof|
|Study Chair:||Michal Mego, prof||National Cancer Institute (NCI)|