scholarly journals Reducing Sample Sizes in Phase II Trials based on Exact Binomial Tests by Shifting Design Parameters

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Dirk Klingbiel
Keyword(s):  
Phase Ii ◽  
Design Parameters ◽  
Sample Sizes ◽  
Phase Ii Trials

scholarly journals Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Matthieu Texier ◽  
Federico Rotolo ◽  
Michel Ducreux ◽  
Olivier Bouché ◽  
Jean-Pierre Pignon ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Phase Ii ◽  
Treatment Effect ◽  
Parametric Method ◽  
Design Parameters ◽  
Nonparametric Method ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
The Times ◽  
The Impact

In early phase clinical trials of cytotoxic drugs in oncology, the efficacy is typically evaluated based on the tumor shrinkage. However, this criterion is not always appropriate for more recent cytostatic agents, and alternative endpoints have been proposed. The growth modulation index (GMI), defined as the ratio between the times to progression in two successive treatment lines, has been proposed for a single-arm phase II trials. The treatment effect is evaluated by estimating the rate of patients having a GMI superior to a given threshold. To estimate this rate, we investigated a parametric method based on the distribution of the times to progression and a nonparametric one based on a midrank estimator. Through simulations, we studied their operating characteristics and the impact of different design parameters (censoring, dependence, and distribution) on them. In these simulations, the nonparametric estimator slightly underestimated the rate and had slightly overconservative confidence intervals in some cases. Conversely, the parametric estimator overestimated the rate and had anticonservative confidence intervals in some cases. The nonparametric method appeared to be more robust to censoring than the parametric one. In conclusion, we recommend the nonparametric method, but the parametric method can be used as a supplementary tool.

scholarly journals Design Issues in Randomized Phase II/III Trials

2012 ◽  
Vol 30 (6) ◽  
pp. 667-671 ◽  
Author(s):  
Edward L. Korn ◽  
Boris Freidlin ◽  
Jeffrey S. Abrams ◽  
Susan Halabi
Keyword(s):  
Phase Ii ◽  
Phase Iii ◽  
Control Treatment ◽  
Design Parameters ◽  
Phase Ii Trials ◽  
Screening Designs ◽  
Randomized Phase Ii ◽  
Adaptive Trial Design ◽  
Target Treatment ◽  
New Treatment

Phase II trials are used to show sufficient preliminary activity of a new treatment (in single-arm designs or randomized screening designs) or to select among treatments with demonstrated activity (in randomized selection designs). The treatments prioritized in a phase II trial are then tested definitively against a control treatment in a randomized phase III trial. Randomized phase II/III trials use an adaptive trial design that combines these two types of trials in one, with potential gains in time and reduced numbers of patients required to be treated. Two key considerations in designing a phase II/III trial are whether to suspend accrual while the phase II data mature and the choice of phase II target treatment effect. We discuss these phase II/III design parameters, give examples of phase II/III trials, and provide recommendations concerning efficient phase II/III trial designs.

Some early phase II trials in previously untreated multiple myeloma: The Royal Marsden experience

2001 ◽  
Vol 38 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Bhawna Sirohi ◽  
Samar Kulkarni ◽  
Ray Powles
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Early Phase ◽  
Phase Ii Trials

Adaptive designs for single-arm phase II trials in oncology

2012 ◽  
Vol 11 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Stefan Englert ◽  
Meinhard Kieser
Keyword(s):  
Phase Ii ◽  
Adaptive Designs ◽  
Phase Ii Trials

Intrathecal Mafosfamide: A Preclinical Pharmacology and Phase I Trial

2005 ◽  
Vol 23 (7) ◽  
pp. 1555-1563 ◽  
Author(s):  
Susan M. Blaney ◽  
Frank M. Balis ◽  
Stacey Berg ◽  
Carola A.S. Arndt ◽  
Richard Heideman ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Trial ◽  
Neoplastic Meningitis ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Studies ◽  
Preclinical Studies ◽  
Phase Ii Trials ◽  
Cytotoxicity Studies

Purpose Preclinical studies of mafosfamide, a preactivated cyclophosphamide analog, were performed to define a tolerable and potentially active target concentration for intrathecal (IT) administration. A phase I and pharmacokinetic study of IT mafosfamide was performed to determine a dose for subsequent phase II trials. Patients and Methods In vitro cytotoxicity studies were performed in MCF-7, Molt-4, and rhabdomyosarcoma cell lines. Feasibility and pharmacokinetic studies were performed in nonhuman primates. These preclinical studies were followed by a phase I trial in patients with neoplastic meningitis. There were five dose levels ranging from 1 mg to 6.5 mg. Serial CSF samples were obtained for pharmacokinetic studies in a subset of patients with Ommaya reservoirs. Results The cytotoxic target exposure for mafosfamide was 10 μmol/L. Preclinical studies demonstrated that this concentration could be easily achieved in ventricular CSF after intraventricular dosing. In the phase I clinical trial, headache was the dose-limiting toxicity. Headache was ameliorated at 5 mg by prolonging the infusion rate to 20 minutes, but dose-limiting headache occurred at 6.5 mg dose with prolonged infusion. Ventricular CSF mafosfamide concentrations at 5 mg exceeded target cytotoxic concentrations after an intraventricular dose, but lumbar CSF concentrations 2 hours after the dose were less than 10 μmol/L. Therefore, a strategy to alternate dosing between the intralumbar and intraventricular routes was tested. Seven of 30 registrants who were assessable for response had a partial response, and six had stable disease. Conclusion The recommended phase II dose for IT mafosfamide, administered without concomitant analgesia, is 5 mg over 20 minutes.

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