Randomized Phase II Trials for Selection: No Prospective Control Arms

2013 ◽  
pp. 105-118
Keyword(s):  
Phase Ii ◽  
Phase Ii Trials ◽  
Prospective Control ◽  
Randomized Phase Ii

Design Issues of Randomized Phase II Trials and a Proposal for Phase II Screening Trials

2005 ◽  
Vol 23 (28) ◽  
pp. 7199-7206 ◽  
Author(s):  
Lawrence V. Rubinstein ◽  
Edward L. Korn ◽  
Boris Freidlin ◽  
Sally Hunsberger ◽  
S. Percy Ivy ◽  
...  
Keyword(s):  
Phase Ii ◽  
False Positive ◽  
Standard Treatment ◽  
False Negative ◽  
Error Rates ◽  
Targeted Treatment ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Treatment Control ◽  
Randomized Phase Ii

Future progress in improving cancer therapy can be expedited by better prioritization of new treatments for phase III evaluation. Historically, phase II trials have been key components in the prioritization process. There has been a long-standing interest in using phase II trials with randomization against a standard-treatment control arm or an additional experimental arm to provide greater assurance than afforded by comparison to historic controls that the new agent or regimen is promising and warrants further evaluation. Relevant trial designs that have been developed and utilized include phase II selection designs, randomized phase II designs that include a reference standard-treatment control arm, and phase II/III designs. We present our own explorations into the possibilities of developing “phase II screening trials,” in which preliminary and nondefinitive randomized comparisons of experimental regimens to standard treatments are made (preferably using an intermediate end point) by carefully adjusting the false-positive error rates (α or type I error) and false-negative error rates (β or type II error), so that the targeted treatment benefit may be appropriate while the sample size remains restricted. If the ability to conduct a definitive phase III trial can be protected, and if investigators feel that by judicious choice of false-positive probability and false-negative probability and magnitude of targeted treatment effect they can appropriately balance the conflicting demands of screening out useless regimens versus reliably detecting useful ones, the phase II screening trial design may be appropriate to apply.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

43 Preoperative chemotherapy in early stage NSCLC: Parallel randomized phase II trials

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S284
Author(s):  
Frank C. Detterbeck ◽  
Mark A. Socinski ◽  
M. Patricia Rivera ◽  
Martin J. Edelman ◽  
Joshua R. Sonett ◽  
...  
Keyword(s):  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Early Stage ◽  
Phase Ii Trials ◽  
Early Stage Nsclc ◽  
Randomized Phase Ii

scholarly journals Resampling the N9741 Trial to Compare Tumor Dynamic Versus Conventional End Points in Randomized Phase II Trials

2015 ◽  
Vol 33 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Manish R. Sharma ◽  
Elizabeth Gray ◽  
Richard M. Goldberg ◽  
Daniel J. Sargent ◽  
Theodore G. Karrison
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Iii ◽  
Rank Test ◽  
Phase Ii Trials ◽  
End Points ◽  
End Point ◽  
Randomized Phase Ii ◽  
Log Ratio

Purpose The optimal end point for randomized phase II trials of anticancer therapies remains controversial. We simulated phase II trials by resampling patients from N9741, a randomized phase III trial of chemotherapy regimens for metastatic colorectal cancer, and compared the power of various end points to detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and oxaliplatin] had longer overall survival than both IROX [irinotecan plus oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]). Methods Tumor measurements and progression-free survival (PFS) data were obtained for 1,471 patients; 1,002 had consistently measured tumors and were resampled (5,000 replicates) to simulate two-arm, randomized phase II trials with α = 0.10 (one sided) and 20 to 80 patients per arm. End points included log ratio of tumor size at 6, 12, and 18 weeks relative to baseline; time to tumor growth (TTG), estimated using a nonlinear mixed-effects model; and PFS. Arms were compared using rank sum tests for log ratio and TTG and a log-rank test for PFS. Results For FOLFOX versus IFL, TTG and PFS had similar power, with both exceeding the power of log ratio at 18 weeks; for FOLFOX versus IROX, TTG and log ratio at 18 weeks had similar power, with both exceeding the power of PFS. The best end points exhibited > 80% power with 60 to 80 patients per arm. Conclusion TTG is a powerful end point for randomized phase II trials of cytotoxic therapies in metastatic colorectal cancer; it was either comparable or superior to PFS and log ratio at 18 weeks. Additional studies will be needed to clarify the potential of TTG as a phase II end point.

scholarly journals Between-Arm Comparisons in Randomized Phase II Trials

2009 ◽  
Vol 19 (3) ◽  
pp. 456-468 ◽  
Author(s):  
Sin-Ho Jung ◽  
Stephen L. George
Keyword(s):  
Phase Ii ◽  
Phase Ii Trials ◽  
Randomized Phase Ii
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