Here is the design of a clinical trial:

Official Title: Validation of Tie2 as the First Tumour Vascular Response Biomarker for VEGF Inhibitors: Optimising the Design of a Subsequent Randomised Discontinuation Trial: VALTIVE1

Included conditions:
- Ovary Cancer

Study Armgroups:

Interventions:

Primary Outcomes:
- {'measure': 'Progression free survival (PFS)', 'description': 'To establish the validity of the Tie2 test as measured by progression free survival by showing the difference in terms of PFS between Tie2 vascular responders and Tie2 vascular non- responders.', 'timeFrame': "Up to 12 months after completion of the last Participant's follow up visit"}

Please estimate the sample size based on the assumption: 
For the bevacizumab only arm, a significance level of 0.05 and a statistical power of 80% are assumed. For the bevacizumab + PARPi arm, a significance level of 0.05 and a power of 90% are assumed. Additionally, a one-sided time dependent Cox-regression analysis is used for the bevacizumab only arm, and a two one-sided t-test (TOST) for equivalence is used for the bevacizumab + PARPi arm. Missing/dropout rates are 10% for the bevacizumab only arm and 10% early progressive disease and 15% loss to follow up for the bevacizumab + PARPi arm.
Sample size
          
            Arm: bevacizumab only
            For the purposes of sample size calculation, survival data were simulated from the survival rate published in the ICON7 trial. Given a group of N simulated patients, with 75% vascular responders and 25% non-responders, the significance of survival difference between vascular responders and non-responders was estimated using a one-sided time dependent Cox-regression analysis, at a significance level of 0.05. The simulation was repeated 1000 times for each different value of N. We sought the minimum N value that would allow detection of significance in 800 simulation runs or more. We intend to recruit 176 patients (160â+â10% to allow for loss to follow up), of which 132 will have a Tie2-defined vascular response and 44 will be non-responders, to allow a statistical power of 80% and a significance level of 0.05 for the detection of an HR of 0.55. As the control arm of the ICON8b trial is the standard of care, we have agreement that up to 50 ICON8b control patientsâ translational research samples and accompanying data would be available for this application. Therefore, in total we need to recruit at least 126 patients.
          
          
            Arm: bevacizumabâ+âPARPi
            In this arm, we will test the hypothesis that olaparib has no impact on the expression level of Tie2 and, therefore, it does not compromise the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab. Accordingly, the null hypothesis for the power calculation is that Tie2 trajectory will not be altered through the addition of olaparib. Based on our ICON7 data, we anticipate that Tie2 has a mean reduction of 0.04 and standard deviation of 0.19 (both on log2 scale) from 9 to 18Â weeks (the estimated period during which olaparib would be added) in patients already receiving bevacizumab. Defining one standard deviation as the acceptance criteria for equivalence, we estimate that a minimum number of 23 participants will be needed to achieve a 90% power at a significance level of 0.05 based on a two one-sided t-test (TOST) for equivalence. We plan to recruit a total of 29 participants for this arm and the control cohort, allowing for 10% of patients who may develop early progressive disease and 15% of patients who may be lost to follow up during the study.