Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma

Cancer ◽  
2010 ◽  
Vol 117 (4) ◽  
pp. 758-767 ◽  
Author(s):  
Brian I. Rini ◽  
Mark Stein ◽  
Pat Shannon ◽  
Simantini Eddy ◽  
Allison Tyler ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Phase 1

P0125 A phase 1/2 trial of BNC105P with everolimus in metastatic renal cell carcinoma

2015 ◽  
Vol 51 ◽  
pp. e26
Author(s):  
S. Pal ◽  
A. Azad ◽  
S. Bhatia ◽  
H. Drabkin ◽  
B. Costello ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase 1

scholarly journals Dose escalation of axitinib on disease progression as a strategy in the treatment of metastatic renal cell carcinoma

ESMO Open ◽  
2018 ◽  
Vol 3 (7) ◽  
pp. e000445 ◽  
Author(s):  
Gary Joseph Doherty ◽  
Deirdre Lynskey ◽  
Athena Matakidou ◽  
Kate Fife ◽  
Tim Eisen
Keyword(s):  
Renal Cell Carcinoma ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Drug Label ◽  
Entire Cohort

IntroductionThe AXIS trial established axitinib as a standard of care treatment for patients with metastatic renal cell carcinoma (mRCC) after failure of a prior tyrosine kinase inhibitor. Axitinib dosing begins at 5  mg twice daily, with escalation of doses to 7  and 10  mg after consecutive 2-week intervals if tolerated (as per the drug label). Given clinical concerns about drug-related toxicity, we have used a pragmatic strategy where dose escalations were made only after disease progression or where rapid responses were clinically required.MethodsWe performed a retrospective review of electronic health records and radiology of all patients with mRCC treated with axitinib for >2 weeks at Addenbrooke’s Hospital, Cambridge, UK, over a 37 -month period to determine the clinical and radiological effects of dose escalations made according to the above strategy.Results42 patients fitting these criteria were identified, 29 having ≥1  dose escalation event (DEE). 60 DEEs were identified (median of two per patient), and the objective radiological consequences of 53 DEEs could be evaluated. The disease control rate (partial response or stable disease) after the first DEE instituted for disease progression was similar to that after the second DEE (68.8% vs 70%). 56.6 % of all DEEs and 63.6 % of DEEs made as a result of disease progression resulted in disease control. The median OS from the commencement of axitinib for all dose-escalated patients was 19.9 months, and 16.5 months for the entire cohort. The mean dose (for all patients) at 90 days after starting axitinib was 5.92  mg.ConclusionThese data suggest that dose escalation of axitinib after disease progression may be an effective dosing strategy for patients with mRCC, and this may be a preferred option in patients in whom there are particular concerns about drug-related toxicity, quality of life optimisation or healthcare-associated costs.

scholarly journals Sunitinib rechallenge with dose escalation in progressive metastatic renal cell carcinoma

Medicine ◽  
2018 ◽  
Vol 97 (31) ◽  
pp. e11565 ◽  
Author(s):  
Xingming Zhang ◽  
Pengfei Shen ◽  
Jin Yao ◽  
Ni Chen ◽  
Jiyan Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell

scholarly journals Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma

Kidney Cancer ◽  
2019 ◽  
Vol 3 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Andreas Bruchbacher ◽  
Sebastian Nachbargauer ◽  
Harun Fajkovic ◽  
Manuela Schmidinger
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell

scholarly journals A phase 1 trial of SGN‐CD70A in patients with CD70‐positive, metastatic renal cell carcinoma

Cancer ◽  
2019 ◽  
Vol 125 (7) ◽  
pp. 1124-1132 ◽  
Author(s):  
Sumanta K. Pal ◽  
Andres Forero‐Torres ◽  
John A. Thompson ◽  
John C. Morris ◽  
Saurabh Chhabra ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase 1 ◽  
Phase 1 Trial

scholarly journals An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti‐Endoglin Antibody) with Axitinib in Patients with Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 24 (2) ◽  
pp. 202-210 ◽  
Author(s):  
Toni K. Choueiri ◽  
M. Dror Michaelson ◽  
Edwin M. Posadas ◽  
Guru P. Sonpavde ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Open Label ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Open Label Phase

Clinical Effect of Dose Escalation After Disease Progression in Patients With Metastatic Renal Cell Carcinoma

2017 ◽  
Vol 15 (2) ◽  
pp. e275-e280 ◽  
Author(s):  
Moshe C. Ornstein ◽  
Laura Wood ◽  
Paul Elson ◽  
Kimberly Allman ◽  
Jennifer Beach ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Clinical Effect

A phase I study of BMS-936558 plus sunitinib or pazopanib in patients with metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2614-TPS2614
Author(s):  
Hans J. Hammers ◽  
Brian I. Rini ◽  
Gary R. Hudes ◽  
Marc S. Ernstoff ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Phase I Study ◽  
Predictive Biomarkers ◽  
Treatment Naïve

TPS2614 Background: Standard treatments for metastatic renal cell carcinoma (mRCC) block the vascular endothelial growth factor pathway (eg, sunitinib, pazopanib) or mammalian target of rapamycin pathway (e.g., temsirolimus, everolimus). However, most patients (pts) develop resistance and complete responses are rare. Upregulation of programmed death-1 (PD-1) in tumor infiltrating lymphoctyes, and its ligand PD-L1 in tumors, is associated with more aggressive disease and poor prognosis. Blocking the PD-1/PD-L1 interaction is a novel immunotherapeutic approach for mRCC. In preliminary results of a phase I trial, the anti-PD-1 monoclonal antibody BMS-936558 had antitumor activity in pts with advanced tumors, including objective responses (ORs) in 6 of 18 pts with mRCC. Here we describe a phase I study planned to evaluate the safety, tolerability, and maximum tolerated dose (MTD) of BMS-936558, when combined with sunitinib or pazopanib in pts with mRCC. Methods: This open-label study will have two parallel treatment arms (BMS-936558 plus sunitinib and BMS-936558 plus pazopanib) conducted in two parts (dose escalation and dose expansion). Pts must have received ≥1 prior systemic therapy to be eligible for dose escalation. Only treatment-naïve pts will be eligible for dose expansion. Up to 36 pts (18 per arm) will be treated in the dose-escalation phase. After determining the MTD of BMS-936558, treatment-naïve pts will be enrolled to expansion cohorts allowing 24 pts to be treated at the MTD of each arm. Each treatment cycle will be 6 weeks, with BMS-936558 dosed on Days 1 and 22 and sunitinib or pazopanib given according to product label. Adverse events will be graded according to NCI CTCAE v4.0. Disease will be assessed every 6 weeks for the first four assessments and then every 12 weeks until disease progression. Pts will be treated until unacceptable toxicity, disease progression, or withdrawal of consent. The safety profile in pts treated at the MTD will be used to determine the recommended phase II study dose of BMS-936558 in each combination arm. Secondary objectives will include OR rate and duration of response based on RECIST 1.1. Exploratory analyses will investigate predictive biomarkers of BMS-936558.

Clinical effect of TKI dose-escalation after disease progression in patients with metastatic renal cell carcinoma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
Moshe Chaim Ornstein ◽  
Paul Elson ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Laura S. Wood ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Metastatic Renal Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Clinical Effect
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