scholarly journals Multicenter, Double-Blind, Randomized, Phase II Trial To Assess the Safety and Efficacy of Ceftolozane-Tazobactam plus Metronidazole Compared with Meropenem in Adult Patients with Complicated Intra-Abdominal Infections

2014 ◽  
Vol 58 (9) ◽  
pp. 5350-5357 ◽  
Author(s):  
Christopher Lucasti ◽  
Ellie Hershberger ◽  
Benjamin Miller ◽  
Sara Yankelev ◽  
Judith Steenbergen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Cure ◽  
Phase Ii Trial ◽  
Success Rates ◽  
Double Blind ◽  
Content Type ◽  
Randomized Phase Ii ◽  
Intent To Treat ◽  
Abdominal Infections ◽  
Event Rates

ABSTRACTCeftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity againstPseudomonas aeruginosaand other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producingEnterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, −12.4%; 95% CI, −34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, −7.1%; 95% CI, −30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success againstEscherichia coli(89.5%),Klebsiella pneumoniae(100%), andP. aeruginosa(100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.)

A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults

2006 ◽  
Vol 1289 ◽  
pp. 303-306 ◽  
Author(s):  
Shelly A. McNeil ◽  
Scott A. Halperin ◽  
Joanne M. Langley ◽  
Bruce Smith ◽  
Darlene M. Baxendale ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Group A Streptococcus ◽  
Healthy Adults ◽  
Double Blind ◽  
Randomized Phase Ii ◽  
Group A

Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
Douglas Adkins ◽  
Jin-Ching Lin ◽  
Assuntina Gesualda Sacco ◽  
Jessica C. Ley ◽  
Peter Oppelt ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Double Blind ◽  
Platinum Resistant ◽  
Randomized Phase Ii

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.

Nintedanib versus placebo in patients receiving mFOLFOX6 for metastatic, chemorefractory colorectal cancer: TRICC-C trial—Final results from the randomized phase II trial of the AIO.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 666-666
Author(s):  
Thomas Jens Ettrich ◽  
Andreas Wolfgang Berger ◽  
Thomas Decker ◽  
Ralf Hofheinz ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Therapeutic Option ◽  
Statistical Significance ◽  
Single Agent ◽  
Second Line ◽  
Double Blind ◽  
Anti Vegf ◽  
Randomized Phase Ii ◽  
Line Setting

666 Background: Anti-VEGF agents plus chemotherapy improve PFS of patients with mCRC in the first- and second-line-setting. During this treatment tumour angiogenesis is driven by other factors but VEGF. Nintedanib, a triple angiokinase inhibitor of VEGFR-1-3, FGFR-1/-3 and PDGFR-α/-β, thereby additionally targets angiogenic escape mechanisms upon resistance to anti-VEGF treatment. The TRICC-C trial evaluates the combination of mFOLFOX6 plus Nintedanib. Final results of the randomized phase II trial are presented. Methods: Patients with mCRC having received one line of non-oxaliplatin containing palliative chemotherapy, with an ECOG-PS of 0/1 were randomized 1:1 in a double-blind design to receive: mFOLFOX6 plus Nintedanib (2 x 200 mg p.o./d, d1-d14) or placebo, respectively, repeated every 14 days. Primary endpoint was PFS. Secondary endpoints were ORR, OS and safety. Patients who received at least one dose of trial medication were included in the efficacy and safety analyses. Results: From 12/2012 to 5/2016 53 patients (scheduled n = 180) were randomized. The trial was terminated prematurely due to slow accrual. Compared to mFOLFOX6 plus placebo (F+P), the combination of mFOLFOX6 plus Nintedanib (F+N) improved mPFS (F+P: 4.6 vs. F+N: 8.1 mo.; HR 0.65; 95% CI 0.32-1.30; p = 0.2156), mOS (F+P: 9.9 vs. F+N: 17.1 mo.; HR 1.03, 95% CI 0.48-2.23; p = 0.9387) and DCR (F+P: 50 vs. F+N: 66,7%; p = 0.2709). ORR was comparable in both arms (F+N: 3.8 vs. F+P: 3.7%). Toxicity was low to moderate without major differences between both arms except G 3/4 neutropenia (F+N: 19%, F+P: 12%) and GI disorders (F+N: 23%, F+P: 15%). Conclusions: Final results suggest a PFS, OS and DCR benefit for mFOLFOX6 + Nintedanib in the second-line therapy of mCRC. Due to the premature termination of the trial there was no statistical significance demonstrable. Showing no clinically significant PFS-benefit in the first-line situation (mFOLFOX6 plus Nintedanib/Bevacizumab, Ann Oncol. 2015) or the last line as single agent, respectively (ESMO 2016) the TRICC-C results suggests that Nintedanib plus mFOLFOX6 could be an interesting therapeutic option for the second-line situation. Clinical trial information: NCT01362361.

scholarly journals EVITA—a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity

2018 ◽  
Vol 29 (4) ◽  
pp. 1010-1015 ◽  
Author(s):  
R.-D. Hofheinz ◽  
S. Lorenzen ◽  
J. Trojan ◽  
J. Ocvirk ◽  
T.J. Ettrich ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Skin Toxicity ◽  
Vitamin K1 ◽  
Double Blind ◽  
Randomized Phase Ii
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