Phase II study of avelumab in multiple relapsed/refractory testicular germ cell cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16045-e16045 ◽  
Author(s):  
Michal Mego ◽  
Daniela Svetlovska ◽  
Michal Chovanec ◽  
Katarina Rejlekova ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Objective Response ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Testicular Tissue ◽  
Testicular Germ Cell ◽  
End Point

e16045 Background: Testicular germ cell tumors (TGCTs) represent a highly curable disease; however, a small proportion of patients develop disease recurrence. PD-L1 expression is significantly higher in germ cell tumors (GCTs) in comparison to normal testicular tissue and high PD-L1 expression is associated with inferior progression-free and overall survival compared to patients with low PD-L1 expression. This study aimed to determine the efficacy and toxicity of PD-L1 antagonist, Avelumab, in patients with refractory GCTs. Methods: From November 2017 to January 2018, 8 patients with refractory GCTs were enrolled in the phase II study. All patients were pretreated with at least 2 cisplatin-based therapies (median 5, range 2 – 6); 5 tumors (62.5%) were absolutely refractory to cisplatin and 5 patients (62.5%) had visceral non-pulmonary metastases. Avelumab was administered at a dose of 10mg/kg biweekly until progression or unacceptable toxicity. The primary end point was 12-weeks progression-free survival (PFS). If < 8 responses to study therapy will be observed among the first 15 patients, the study will be terminated. Results: Median age was 29 years (range: 22 – 52 years). During a median follow-up period of 2.6 months (range: 0.3 - 14.4), 7 (87.5%) patients experienced disease progression and 6 patients (80.0%) died. Twelve-week PFS was 0%, median PFS was 1.4 months, 95%CI (0.9 – 1.4) and median OS was 2.7 months, 95% CI (1.0 – 3.3). No objective response was observed. Avelumab was well tolerated, no severe adverse event was observed. Conclusions: This study failed to achieve its primary end point and our data suggest lack of Avelumab efficacy in unselected multiple relapsed/refractory TGCTs. Clinical trial information: NCT03403777.

Phase II study of gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumors (GCTs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17009-e17009
Author(s):  
Michal Mego ◽  
Daniela Svetlovska ◽  
Maria Reckova ◽  
Katarina Kalavska ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Partial Remission ◽  
Phase Ii Study ◽  
Parp Inhibitor ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Median Number ◽  
Early Event ◽  
End Point

e17009 Background: GCTs represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. PARP is overexpressed in GCTs compared to normal testis and PARP overexpression is early event in GCTs development. Gemcitabine and carboplatin showed activity in refractory GCTs. This study aimed to determine the efficacy and toxicity of gemcitabine, carboplatin and PARP inhibitor, veliparib, in patients with multiple relapsed/refractory GCTs. Methods: Fifteen patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from October 2016 to October 2020. All patients were pretreated with at least 2 cisplatin-based therapies (median 2, range 2 – 4); 3 tumors (20.0%) were absolutely refractory to cisplatin and 5 patients (33.3%) had visceral non-pulmonary metastases. Gemcitabine was administered at a dose 800mg/m2 day 1 and 8 every 3 weeks; carboplatin AUC = 4, day 1, every 3 weeks and veliparib 250mg bid day continuously. The primary end point was 12-months progression-free survival (PFS), if < 8 patients experienced 12-months PFS, the treatment will be considered ineffective. Results: Median age was 31 years (range: 22 – 48 months). Median number of treatment cycles was 4 (range 2 – 8). During a median follow-up period of 9.2 months (range: 1.9 – 23.8), all (100%) patients experienced disease progression and 14 patients (93.3%) died. Twelve-months PFS was achieved in 1 (6.7%) patient. Median PFS was 3.1 months, 95%CI (2.2 – 3.9) and median OS was 10.5 months, 95% CI (8.9 – 11.1). Partial remission was observed in 4 (26.7%) and disease stabilization in 5 (33.3%) of patients. Favorable response (complete or partial remission with negative serum tumor markers) experienced 3 (20%) patients. Treatment was well tolerated, however, 12 (80%) of patients experienced grade 3/4 neutropenia, 9 (60%) anemia, 14 (93.3%) thrombocytopenia and 2 (13.3%) febrile neutropenia. Conclusions: This study failed to achieve its primary end point and our data suggest limited efficacy of gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumors. Clinical trial information: NCT02860819.

Phase II study of everolimus (E) in refractory testicular germ cell tumors (TGCTs).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Michal Mego ◽  
Daniela Svetlovska ◽  
Vera Miskovska ◽  
Jana Obertova ◽  
Peter Zuzak ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Phase II Trial of Gemcitabine in Refractory Germ Cell Tumors

1999 ◽  
Vol 17 (2) ◽  
pp. 509-509 ◽  
Author(s):  
Lawrence H. Einhorn ◽  
Michael J. Stender ◽  
Stephen D. Williams
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Germ Cell Tumors ◽  
Late Relapse ◽  
Tumor Patient ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE: This phase II study was designed to determine the toxicity and activity of single-agent gemcitabine in heavily pretreated patients with germ cell tumors.PATIENTS AND METHODS: From March 1996 through November 1997, 21 patients were enrolled onto a phase II study of gemcitabine 1,200 mg/m2, given on days 1, 8, and 15 every 4 weeks. One patient was unassessable because he never received any gemcitabine. Thirteen of 20 patients had received three prior regimens, and 13 patients were platinum refractory (progression during or within 4 weeks of platinum treatment). There were five extragonadal cases and two patients with late relapse (relapse beyond 2 years).RESULTS: Gemcitabine was well tolerated. Only one patient had grade 3 or 4 nonhematologic toxicity (grade 3 nausea). Six of 20 patients had grade 3 leukopenia. There were no episodes of granulocytopenic fever, and no patient required platelet transfusion. Three (15%) of 20 patients achieved an objective response, including one complete remission. Three additional patients had a minor radiographic or serologic response.CONCLUSION: Gemcitabine had definite activity in this heavily pretreated germ cell tumor patient population.

Phase II study of everolimus in refractory testicular germ cell tumors

2016 ◽  
Vol 34 (3) ◽  
pp. 122.e17-122.e22 ◽  
Author(s):  
Michal Mego ◽  
Daniela Svetlovska ◽  
Vera Miskovska ◽  
Jana Obertova ◽  
Patrik Palacka ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

scholarly journals Prognostic Value of Apoptosis-Inducing Factor (AIF) in Germ Cell Tumors

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 776
Author(s):  
Katarina Letkovska ◽  
Pavel Babal ◽  
Zuzana Cierna ◽  
Silvia Schmidtova ◽  
Veronika Liskova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Nuclear Translocation ◽  
Malignant Tumors ◽  
Expression Patterns ◽  
Germ Cell Tumors ◽  
Testicular Tissue ◽  
Testicular Germ Cell ◽  
Visceral Metastases ◽  
Apoptosis Inducing Factor ◽  
Clinicopathological Variables

Apoptosis is a strictly regulated process essential for preservation of tissue homeostasis. This study aimed to evaluate expression of apoptosis inducing factor (AIF) in testicular germ cell tumors (GCTs) and to correlate expression patterns with clinicopathological variables. Formalin-fixed and paraffin-embedded specimens of non-neoplastic testicular tissue and GCTs obtained from 216 patients were included in the study. AIF expression was detected by immunohistochemistry, scored by the multiplicative quickscore method (QS). Normal testicular tissue exhibits higher cytoplasmic granular expression of AIF compared to GCTs (mean QS = 12.77 vs. 4.80, p < 0.0001). Among invasive GCTs, mean QS was the highest in embryonal carcinoma, yolk sac tumor and seminoma, lower in teratoma and the lowest in choriocarcinoma. No nuclear translocation of AIF was observed. Nonpulmonary visceral metastases were associated with lower AIF expression. Metastatic GCTs patients with high AIF expression had better overall survival compared to patients with low AIF expression (HR = 0.26, 95% CI 0.11–0.62, p = 0.048). We observed significantly lower AIF expression in GCTs compared to normal testicular tissue, which is an uncommon finding in malignant tumors. AIF downregulation might represent one of the mechanisms of inhibition of apoptosis and promotion of cell survival in GCTs.

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

scholarly journals A multi-center prospective phase II study of high-dose chemotherapy in germ-cell cancer patients relapsing from complete remission

1999 ◽  
Vol 10 (12) ◽  
pp. 1467-1474 ◽  
Author(s):  
S. Rodenhuis ◽  
R. de Wit ◽  
P.H.M. de Mulder ◽  
H.J. Keizer ◽  
D.T. Sleijfer ◽  
...  
Keyword(s):  
Complete Remission ◽  
Germ Cell ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
High Dose Chemotherapy ◽  
Germ Cell Cancer ◽  
High Dose ◽  
Prospective Phase

Phase II Trial of Weekly Intravenous Gemcitabine With Continuous Infusion Fluorouracil in Patients With Metastatic Renal Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2419-2426 ◽  
Author(s):  
Brian I. Rini ◽  
Nicholas J. Vogelzang ◽  
Mary C. Dumas ◽  
James L. Wade ◽  
David A. Taber ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Renal Cell ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Metastatic Rcc

PURPOSE: To determine the clinical response rate of the combination of weekly intravenous (IV) gemcitabine with continuous infusion fluorouracil (5-FU) in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between June 1998 and February 1999, 41 patients with metastatic RCC were enrolled onto this multi-institutional phase II study of gemcitabine 600 mg/m2 over 30 minutes on days 1, 8, and 15 and 5-FU 150 mg/m2/d via continuous IV infusion through a permanent catheter on days 1 to 21 of a 28-day cycle. Patients had a Cancer and Leukemia Group B performance status of 0 or 1, with a median time since diagnosis of metastatic disease of 10 months (range, 0 to 129 months). Thirty-three patients (80%) had multiple metastatic sites, and 34 patients (83%) had prior chemotherapy or immunotherapy. RESULTS: Of the 39 assessable patients, there were no complete responses but seven partial responses (objective response rate = 17%; 95% confidence interval, 8% to 34%). Five minor responses (25% to 50% decreased tumor size) were also observed. The duration of response for the seven partial responders was 2, 3, 7, 8, 10, 11, and 14 months. Median progression-free survival for the gemcitabine/5-FU group was 28.7 weeks versus 8 weeks for a similar cohort of patients treated on previous phase II studies at the University of Chicago (P = .008). The regimen was well tolerated, with fatigue, mucositis, nausea/vomiting, and grade 2 hematologic toxicities being most common. CONCLUSION: Weekly gemcitabine with continuous infusion 5-FU is an active combination in patients with metastatic RCC. Therapy was well tolerated and produced an improvement in progression-free survival over historical controls.

A Phase II Study of High-Dose Cisplatin, Vinblastine, Bleomycin, and Etoposide (PVeBV Regimen) in Malignant Nondysgerminomatous Germ-Cell Tumors of the Ovary

1994 ◽  
Vol 54 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Stéphane Culine ◽  
Joseph Kattan ◽  
Catherine Lhomme ◽  
Pierre Duvillard ◽  
Guy Michel ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Germ Cell Tumors ◽  
High Dose
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