Sovesudil (locally acting rho kinase inhibitor) for the treatment of normal‐tension glaucoma: the randomized phase II study

2021 ◽  
Author(s):  
Ahnul Ha ◽  
Young Kook Kim ◽  
Jin Wook Jeoung ◽  
Sanjeev Satyal ◽  
Jaesoon Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Rho Kinase ◽  
Normal Tension Glaucoma ◽  
Randomized Phase Ii ◽  
Rho Kinase Inhibitor

Erlotinib beyond progression study: Randomized phase II study comparing chemotherapy plus erlotinib with chemotherapy alone in EGFR tyrosine kinase inhibitor (TKI)-responsive, non-small cell lung cancer (NSCLC) that subsequently progresses.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8114-8114 ◽  
Author(s):  
Balazs Halmos ◽  
Nathan A. Pennell ◽  
Gregory Alan Otterson ◽  
Shirish M. Gadgeel ◽  
Tarek Mekhail ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cox Regression ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Causal Attribution ◽  
Female Gender ◽  
Patient Characteristics ◽  
Resistance Mechanisms ◽  
Cox Regression Analysis ◽  
Randomized Phase Ii

8114 Background: In EGFR-TKI responsive NSCLC, at progression only some tumor clones might carry resistance mechanisms. This provides a rationale for maintenance therapy with TKIs on progression and is supported by “tumor flares” noted in patients taken off of TKI therapy. Methods: Randomized, phase II study of chemotherapy (pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) in patients with progressive NSCLC following clinical benefit from erlotinib for > 12 weeks. In Arm A Pemetrexed or Docetaxel were given at standard doses every 3 weeks to a maximum of 8 cycles. In Arm B chemotherapy was given with ERL at 150 mg oral daily dose on days 2-19 of each cycle. The primary endpoint was that continuation ERL in this patient population could extend PFS by 50%, from 3 to 4.5 months. The original enrollment goal was 39 pts per arm to allow 80% power to detect such a difference. Results: 46 patients were randomized (Arm A: 24; Arm B: 22). Early termination was due to slow enrollment. Patient characteristics were well balanced except for more females on Arm A (p=0.075). The median PFS on Arm A was 5.4 months and for Arm B was 4.6 months (p=0.569). The median overall survival (OS) on Arm A was 18.7 months and for Arm B 14.7 months (p=0.295). Multiple Cox regression analysis showed an impact of female gender on OS (HR 0.1) but not PFS (HR=0.49). EGFR status was available on 39/46 patients. 17 patients in Arm A and 14 Arm B were mutation positive. In analyzing mutation + only patients, no difference in PFS (p=0.332) or OS (p=0.346) was seen amongst the 2 groups. In the mutation + patients the 6 months PFS for Arm A was 39% and for Arm B was 32%. More toxicity was seen on Arm B as compared to Arm A. Irrespective of causal attribution, 1 grade 5 event occurred on Arm A as opposed to 2 events on Arm B. A total of 7 grade 3/4 events occurred on Arm A while 24 occurred on Arm B. Conclusions: No benefit was seen with the continuation of ERL in addition to chemotherapy as compared to chemotherapy alone in patients who had previously benefited from ERL but then showed progression. The combination arm showed significantly more toxicity. Clinical trial information: NCT00660816.

Randomized phase II study of docetaxel plus vandetanib (D+V) versus docetaxel followed by vandetanib (D-V) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (OC): SWOG S0904.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5015-5015 ◽  
Author(s):  
Robert L. Coleman ◽  
James Moon ◽  
Anil Sood ◽  
Donna Branham ◽  
James Edwin Delmore ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Primary Therapy ◽  
Antitumor Effects ◽  
Angiogenic Therapy ◽  
Randomized Phase Ii ◽  
Therapy Stratification

5015 Background: Antiangiogenesis therapy has led to antitumor effects both preclinically and clinically. Vandetanib (V) is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET. These targets are of interest in OC care, as targeting has shown anti-tumor efficacy, particularly in combination with taxanes. We explored the efficacy, safety, and toxicity of docetaxel (D) and V in women with recurrent OC. Methods: Women with resistant, refractory, or progressive/persistent OC were eligible for this randomized phase II study provided they had not received D or V for recurrent disease. Patients were allowed to receive other anti-VEGF targeted agents for primary therapy (stratification variable). Up to 3 additional cytotoxic regimens for recurrence were allowed. Patients were allocated 1:1 to D(75 mg/m2, I.V.)+V (100 mg daily, p.o.) or D(75 mg/m2). Patients receiving single agent D were allowed to crossover to V upon progression (D-V). The primary endpoint was PFS. Other objectives were: OS, objective response (ORR), and frequency/severity of adverse events. The study was designed with 84% power to detect a 1.55 PFS hazard ratio using a one-sided P of 0.1. Results: 131 patients were enrolled; 5 were excluded (1 ineligible, 4 eligible but untreated). 9% had received prior anti-angiogenic therapy. 61 patients on D+V were assessable for toxicity; 19 (31%) had treatment-related G4 events, primarily hematologic. Similarly, 17 (26%) of 65 patients receiving D alone had G4 events, primarily hematologic. 34 (52%) patients crossed over to V; no G4 events were recorded among 32 evaluable patients. G3 diarrhea was observed in 14% of D+V patients; 5% D-V patients. G3 acneiform rash occurred in 2% and 0%, respectively. The median PFS estimates were 3.0 mos (D+V) vs 3.5 (D-V); HR (PFS): 0.98 (80% CI:0.75-1.27). For OS, the median estimates were 14 mos (D+V) vs 12 mos (D-V); HR (OS):0.84 (80% CI:0.56-1.28). ORR was 14% and 17%, respectively. Crossover V response was 4% (1/27 measurable patients). Conclusions: D+V was well tolerated in this population however, did not prolong PFS with respect to D.

Randomized phase II study of dacarbazine with or without sorafenib in patients with advanced melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8511-8511 ◽  
Author(s):  
D. F. McDermott ◽  
J. A. Sosman ◽  
F. S. Hodi ◽  
R. Gonzalez ◽  
G. Linette ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Survival Data ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Advanced Melanoma ◽  
Controlled Study ◽  
Eligibility Criteria ◽  
Randomized Phase Ii

8511 Background: Sorafenib (SOR), a potent and selective multi-kinase inhibitor, exerts its anti-tumor and anti-angiogenic effects via inhibition of VEGFR-1, -2, -3, PDGFR-a, -β, and Raf. Dacarbazine (DTIC) is an FDA-approved cytotoxic agent for advanced melanoma. Phase I/II results of SOR + DTIC were encouraging and prompted this randomized phase II study. Methods: This was a multi- center, double-blinded, placebo-controlled study; eligibility criteria included measurable disease by RECIST, no prior cytotoxic chemotherapy, and no active brain metastases. Advanced melanoma patients (pts) stratified by stage (unresectable III vs IVM1a/M1b vs M1c) and ECOG PS (0 vs 1) were randomized to receive DTIC 1,000 mg/m2 q 21 days + oral placebo (PL) or oral SOR 400 mg bid continuously until the occurrence of progressive disease or intolerable toxicity. The primary endpoint was progression-free survival (PFS) of DTIC+SOR vs DTIC+PL. Using a two-sided test with a = 0.05, 77 PFS events were needed to detect a hazard ratio (HR) of 0.5 (SOR/PL) with 86 % power. The secondary endpoint was overall survival and tertiary endpoints were objective response rate (ORR), time to progression, and duration of response. Results: 101 pts were enrolled over 12 months (51 DTIC+SOR, 50 DTIC+PL). Treatment arms were balanced for age (median 58 yrs), gender (male 70%), PS (ECOG 1 39%), stage (Stage IV M1c 52%) and baseline LDH (>ULN 29%). At the time of analysis by independent assessment, the median PFS of DTIC+PL vs DTIC+SOR was 11.7 wks (95% CI 6.1, 17.9) vs 21.1 wks (95% CI: 16, 28); HR 0.67 [p=0.07]; PFS rate at Day 180 was 18% vs 41%; and ORR was 12% vs 24%. Survival data are immature. Toxicities of Grade 3 or higher (DTIC+PL vs DTIC+SOR) included neutropenia (12% vs 33%), leukopenia (6% vs 14%), thrombocytopenia (18% vs 35%), thrombosis/embolism (0% vs 6%), hypertension (0 vs 8%), hand-foot skin reaction (0 vs 4%), and CNS hemorrhage (0% vs 8%). 3 of the 4 pts with CNS hemorrhage had new brain metastases. No treatment-related deaths occurred in either arm. Conclusions: DTIC+SOR was well tolerated and showed a strong efficacy trend compared with DTIC+PL in median PFS, PFS rate at 6 months and ORR in chemotherapy-naïve pts with advanced melanoma. This regimen warrants further evaluation in larger clinical trial settings. No significant financial relationships to disclose.

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