Open label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: The Greko II study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5577-5577 ◽  
Author(s):  
Jesús García-Donas ◽  
Laia Garrigos ◽  
Nuria Lainez ◽  
Ana Santaballa ◽  
Andres Redondo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Granulosa Cell ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Locally Advanced ◽  
Sample Size Calculation ◽  
Open Label ◽  
Clinical Benefit Rate ◽  
Open Label Phase ◽  
The Impact

5577 Background: Granulosa-cell tumors (GCT) of the ovary are a rare entity characterized by presenting a punctual mutation at the FOXL2 gene 402C→G (C134W). Such mutation leads to a disregulation and overstimulation of the steroidogenic pathway and, ultimately, hormone overproduction. A prior trial by our group (GREKO I trial-GETHI 2011-03; NCT01584297) showed promising activity of ketoconazole, a CYP17 inhibitor used to control steroidogenesis in several conditions. Thus, we aimed to assess the activity of Orteronel (TAK700), a selective inhibitor of 17, 20-lyase, in GCT. Methods: An open-label phase II single arm clinical trial was designed for women with metastatic or locally advanced non-resectable GCT who harbored the somatic mutation FOXL2 402C→G (C134W) and who had not received prior treatment with any CYP17 inhibitor. Treatment consisted on Orteronel 300mg BID, given orally, continuously in a 28-day treatment cycle. The primary objective was clinical benefit rate; secondary objectives were response rate, progression free and overall survival, assessment of the impact of Orteronel in reducing hormonal overproduction and toxicity. Sample size calculation was based on a two stage Simon´s design. A power of 80% was set to differentiate between a 5% and a 25% clinical benefit rate. 20% of losses had been assumed thus 20 patients were scheduled to be enrolled. Results: Since 30/06/2014 to 11/01/2017 10 patients have been included in 9 participating institutions members of Spanish Group for Research in Orphan and Unfrequent Tumors (GETHI). Due to a low recrutiment rate the study was terminated early. Median PFS was 3 months 95%CI (0-12) with 3 patients achieving disease stabilization longer than 12 months. 2 patients remain on treatment after 16 and 14 months. Clinical benefit rate (CR + PR + SD) was 50%, 95%CI (19%-81%). Seven patients have progressed and 2 have died. Only 6 suspected unresected adverse reactions (SUSARs) have been communicated so far (chest pain, fever, febrile neutropenia, eosinophila, neutropenia and anemia). Conclusions: Orteronel achieved a significant clinical benefit in advanced GCT with an favorable toxicity profile. Clinical trial information: NCT02101684.

Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced nonresectable granulosa cell ovarian tumors: The GREKO II study.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS5626-TPS5626
Author(s):  
Alicia Hurtado ◽  
Jesús García-Donas ◽  
Laia Garrigos ◽  
Nuria Laínez ◽  
Andres Redondo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Granulosa Cell ◽  
Phase Ii ◽  
Ovarian Tumors ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Open Label Phase

Interim analysis of a phase II study of nivolumab combined with ipilimumab in patients with pediatric solid tumors in adulthood (GETHI021).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2613-2613 ◽  
Author(s):  
Xabier Mielgo ◽  
Robert Diaz-Beveridge ◽  
Juan Manuel Sepulveda ◽  
Estela Pineda ◽  
Maria Jose Lecumberri ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Therapeutic Options ◽  
Open Label ◽  
Childhood Malignancies

2613 Background: Solid pediatric tumors that appear in adulthood are a heterogeneous group characterized by a low incidence, lack of standard therapeutic options and reduced survival. We have designed the first phase II clinical trial of nivolumab and ipilimumab in this setting, Here, we present the results of the first cohort with 30 evaluable patients. Methods: This is a multicenter, open-label, single arm Phase II study conducted in 15 centers of the Spanish Group for Rare Cancer (GETHI). We aimed to evaluate efficacy and safety of the combination of nivolumab and ipilimumab in adult patients ( 18 years) with locally advanced or metastatic childhood malignancies that have progressed or are not candidates to standard therapy. Treatment consisted on nivolumab 3 mg/kg IV q2w + ipilimumab 1 mg/kg IV q6w for 6 months or until progression/unacceptable toxicity, for a maximum of 24 months. Primary endpoint was overall response rate (ORR) according to RECIST v1.1 criteria. We used a Simon optimal two-stage design, with a first stage including first 30 evaluable patients. Results: 20 patients were male and median age was 43 (range 20-75). Most frequent histologies were medulloblastoma (4) neuroblastoma (4) and Ewing family tumors (3). 90% had received prior systemic therapy with 37% presenting progressive disease as best response. Median previous treatment lines were 3 (range 1-9). 27 patients were PS0-1, and 3 PS2. 6 patients have been treated for ≥6 months . Only one discontinued for adverse events. With a median follow up of 4,3 months (range 0,4-11,3), 1 patient has achieved a deep partial response (PR) (3,6%), 10 stable disease (SD) (35,7%) and 17 progressive disease (PD) (60,7%). 2 patients died before radiologic evaluation. Clinical benefit rate (CR+PR+SD) was 39,3%. Median progression free survival (PFS) was 1,8 months (95% CI 1,3-2,3), with a 3-months-PFS of 32,7% and 6-months-PFS of 20%. Median overall survival (OS) was 6,8 months (95% CI 3,3-10,2). 12 (40%) patients presented adverse events (AE) of any grade and 6 (20%) experienced a grade AE deemed as possibly related to treatment. Conclusions: The combination of nivolumab and ipilimumab showed significant clinical benefit in this population with little therapeutic options. One case of metastatic esthesioneuroblastoma, achieved a dramatic tumor response and represents the first patient with this extremely rare histology treated with immunotherapy. Clinical trial information: EudraCT 2016-003946-99.

Open label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: The Greko II study—GETHI 2013-01.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. TPS5612-TPS5612
Author(s):  
Jf. Rodriguez-Moreno ◽  
Jesús García-Donas ◽  
Laia Garrigos ◽  
Nuria Laínez ◽  
Ana Santaballa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Granulosa Cell ◽  
Phase Ii ◽  
Ovarian Tumors ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Open Label Phase

Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced nonresectable granulosa cell ovarian tumors: The GREKO II study.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. TPS2598-TPS2598
Author(s):  
Laia Garrigos ◽  
Ana Santaballa ◽  
Alicia Hurtado ◽  
Juan Francisco Rodriguez-Moreno ◽  
Ricardo Sanchez-escribano ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Granulosa Cell ◽  
Phase Ii ◽  
Ovarian Tumors ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Open Label Phase

REGOMA: A Randomized, Multicenter, Controlled Open-Label Phase II Clinical Trial of Regorafenib Compared to Lomustine in Relapsed Glioblastoma Patients

2018 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Gian Luca De Salvo ◽  
Alba Ariela Brandes ◽  
Marica Eoli ◽  
Roberta Rudà ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Open Label Phase

scholarly journals OS2.3 Updated results of REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating regorafenib in relapsed glioblastoma patients

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii219-iii219
Author(s):  
G Lombardi ◽  
G de Salvo ◽  
R Rudà ◽  
E Franceschi ◽  
M Eoli ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Open Label Phase

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

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