Multicenter sequential phase II study of flavopiridol plus oxaliplatin (Alvocidib) with or without 5-FU and leucovorin (LV) for patients (pts) with refractory germ cell tumors (GCT) including late relapse (LR).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Darren Richard Feldman ◽  
Walter Michael Stadler ◽  
Leonard Joseph Appleman ◽  
David I. Quinn ◽  
Brian Addis Costello ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Late Relapse ◽  
High Dose ◽  
Stage Design ◽  
Previously Treated ◽  
Tumor Biopsies ◽  
Sequential Phase

364 Background: Flavopiridol + FOLFOX showed activity in refractory GCT pts in a phase I trial (Rathkopf, Clin Cancer Res, 2009). This phase II study assessed the efficacy of this regimen in refractory GCT and the necessity of including 5-FU/LV. Methods: Previously treated pts with progressive GCT were eligible if they had received or were not candidates for high-dose chemotherapy (HDCT). Pts on Arm A received flavopiridol 70mg/m2 plus oxaliplatin 85mg/m2. Arm B (flavopiridol + FOLFOX) tested identical doses of flavopiridol and oxaliplatin plus 5-FU (400mg/m2 bolus, then 1800mg/m2 over 48 hours) and LV 400mg/m2. Treatment was every 2 weeks in 6-week cycles. The primary endpoint was response rate (RR) by RECIST. An identical Simon 2-stage design was used for each arm to differentiate between a RR ≥40% vs. ≤20%, with arm B opening only if arm A was ineffective. With ≥3 responses among the first 12 pts, another 13 pts would be enrolled with responses in ≥8/25 pts needed to show efficacy. Tumor biopsies pre-, during, and post-treatment were assessed by IHC for p53, p21, and cleaved caspase-3. Results: Of 36 pts (7 arm A, 29 arm B), 33 had nonseminoma. Primary site was testis in 27 and mediastinum in 7; 22 pts had received prior HDCT and 13 had LR (>2 years), including 2 on arm A and 11 on arm B. Arm A closed early after 0/7 pts responded (2 SD). Of 25 evaluable pts on arm B, 6 achieved a PR, 9 had SD, and 10 had PD. Notably, 5/10 evaluable LR pts on Arm B had a PR, including 1 pathologic CR, 1 PR-negative markers who received radiation (RT) to a residual bone metastasis, and 1 PR-positive markers who received RT to a residual nodal mass. These 3 pts remain disease-free ≥19 months (m) post-chemotherapy and ≥17m post-RT or surgery. Median PFS and OS were 2.3m and 7.3m for all pts and 3.2m and 11.2m for arm B pts. There was 1 treatment-related death due to sepsis. Conclusions: Although neither arm met the prespecified endpoint, flavopiridol plus FOLFOX (arm B) was particularly active in LR pts, with a 50% overall RR, including several durable responses. Further study of FOLFOX with or without flavopiridol is warranted in LR pts. Correlative data will be presented. Clinical trial information: NCT00957905.

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

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

Phase II-study of sequential high-dose-chemotherapy with paclitaxel, ifosfamide, carboplatin, etoposide( P-ICE) in patients with relapsed or refractory germ cell tumors (GCT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4552-4552
Author(s):  
Thomas Kegel ◽  
Franziska Cygon ◽  
Fabian Maximilian Meinert ◽  
Khaled Hammad ◽  
Frank Steinbach ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Bone Marrow Toxicity ◽  
Good Tolerability ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Ecog Ps

4552 Background: High-dose chemotherapy (HD-CTx) is an active option for salvage chemotherapy in patients (pts) with refractory or relapsed GCT. All previous trials with HD-CTx used one or two cycles of high dose chemotherapy (CTx) including 2 or a maximum of 3 drugs. Another potentially more active option is the application of four sequential HD-CTx cycles (Schmoll et al, JCO 2003). Methods: We conducted a phase II trial of 1(-2) cycle(s) induction CTx with standard dose P-ICE (Paclitaxel 135mg/m² d1, Ifosfamide 1500mg/m² d1-3, Carboplatin 150mg/m² d1-3, Etoposide 150mg/m² d1-3), followed by 4 sequential cycles of HD-P-ICE (Paclitaxel 200mg/m² d1, Ifosfamide 3300mg/m² d1-3, Carboplatin 330mg/m² d1-3, Etoposide 330mg/m² d1-3). Eligibility criteria: relapse or progression under one or more induction CTx, ECOG PS (0-1), Creatinine-clearance > 30ml/min, adaequate liver function, measurable tumor or at least marker-elevation. Results: 37 pts entered the trial and 33 are evaluable (4 pts never received HD-CTx due to lack of stem cells (3) or medical reasons (1)). Prior CTx:1 (N = 26), 2 (N = 4), 3 (N = 3); primary extragonadal: 6; seminoma/ non-seminoma 5/28; ECOG-PS: 0 (19), 1 (14). Response rate: CR/NED 17 (51.5%), CR/NED/PR-/SD- with marker normalization 21 (63.6%), PD 12 (36.4%). DFS of CR/NED: median 59 (8-105) months; RFS of all favourable responders 60 (8-105) months, PFS total 46 (2-105) months. OS for all pts. 51 (6-105) months, OS Favourable Responders: 65 (23 – 105), Nonfavourable Responders: 11 (6-27) months,. Toxicity was tolerable without treatment related death, with mainly grade 4 bone-marrow toxicity and grade 2 mucositis and/or diarrhea. Conclusions: Sequential HD-CTx with one cycle of SD-P-ICE and four cycles HD-CTx is feasible with acceptable toxicity and favourable efficacy. Sequential HD-CTx using the four most active drugs might be a potentially option for this pts-population due to good tolerability, applicability and interesting long-term outcome. Comparison of the standard approach with 1 to 3 sequential high dose cycles of Carboplatin/Etoposide is ongoing (TIGER-Trial). Clinical trial information: EUDRA-CT: 2006-006004-11.

Outcome in 41 patients with late relapse germ cell tumors (GCT) treated with high-dose chemotherapy (HDCT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5086-5086
Author(s):  
A. Lorch ◽  
O. Rick ◽  
J. T. Hartmann ◽  
B. Metzner ◽  
A. Glasmacher ◽  
...  
Keyword(s):  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Late Relapse ◽  
High Dose ◽  
Multifocal Disease ◽  
Very High

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2 and cyclophosphamide 6,400 mg/m2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.

Olaparib as salvage treatment for advanced germ cell tumors after chemotherapy failure: Results of the open-label, single-arm, IGG-02 phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5058-5058
Author(s):  
Ugo De Giorgi ◽  
Giuseppe Schepisi ◽  
Giorgia Gurioli ◽  
Carmela Pisano ◽  
Umberto Basso ◽  
...  
Keyword(s):  
Dna Repair ◽  
Germ Cell ◽  
Phase Ii ◽  
Survival Probability ◽  
Phase Ii Trial ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Open Label

5058 Background: Therapeutic options for patients with advanced germ cell tumors (GCTs) after multiple relapses or resistant disease are limited. Olaparib is an inhibitor of poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. We aimed to evaluate olaparib activity in patients with refractory GCT. Methods: In this proof-of principle open-label, single-arm, phase II trial of olaparib 300 mg twice daily in patients with relapsed/refractory metastatic germ cell cancer IGG-02 study (NCT02533765), patient eligibility included failure after high-dose chemotherapy or after at least 2 different cisplatin-based regimens. Measurements of serum tumor markers and computed tomography were carried out at baseline and every 6 weeks of olaparib treatment. The study primary endpoint was the overall response rate, the study planned to recruit initially 18 patients and not continue further recruitment until one or more responses were observed. Results: Between September 2015 and February 2019, 18 patients, median age 39 years (range, 22-61) were enrolled. The number of prior chemotherapy regimens was: 2 for 3 patients (16.7%), 3 for 5 patients (27.8%), >3 for 10 patients (55.6%). Sixteen cases (89.9%) received prior high-dose chemotherapy with support of hematopoietic progenitor cells. Grade 3-4 adverse events were observed in 5 patients (27.7%). There were no partial responses, 5 cases (27.8%) with stable disease (SD) lasting 3, 4, 4, 7 and 7+ months and 13 (72.2%) progressive disease. The 12-week progression-free survival probability was 27.8% [95% confidence interval (CI): 10.1%-48.9%]. The 12-month overall survival probability was 27.8% (95% CI: 10.1%-48.9%). A germline DNA repair profile panel showed only a BRCA1 mutated case associated with a SD lasted 4 months. Conclusions: Olaparib as a single agent has marginal activity in heavily pretreated GCT patients, however, an anecdotic 4-month SD in the only BRCA mutated patient has been reported. Plans for future studies with olaparib are suggested in combination or following salvage chemotherapy in less pretreated and more selected GCT patients. The Study has been conducted with AstraZeneca contribution. Clinical trial information: NCT02533765 .

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