Scientific intelligence platform for AI-powered data management and workflow automation

A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma

**Objective: **To assess the efficacy and safety of Sunitinib® in recurrent ovarian, fallopian tube and peritoneal carcinoma.

**Year:** 2013

**Source:** Gynecologic Oncology, Volume 128, Issue 2

**Link:** https://www.sciencedirect.com/science/article/pii/S009082581200652X

**Protocol:** https://clinicaltrials.gov/ct2/show/NCT00768144

**Clinical Area:** Oncology

Sample Size Section in Paper/Protocol: |

“This study used a two-stage design to evaluate efficacy of sunitinib based on overall |

Summary of Necessary Parameter Estimates for Sample Size Calculation:

Parameter |
Value |

Significance Level, ⍺ | 0.05 |

Maximum Ineffective Proportion, 𝜋 0 | 0.05 |

Minimum Efficacy Proportion, 𝜋 1 | 0.2 |

Power | 85% |

Design Criterion | Minimax (Note: This was not explicitly stated in the protocol) |

**Step 1: **Select the

This can be done using the radio buttons or alternatively, you can **use the search bar** at the end of the Select Test window.

**Step 2:**Enter the parameter values for sample size calculation taken from the study design. The required sample size will automatically calculate once values for ⍺, 𝜋 0 , 𝜋 1 and Power are entered. (Note that the “Optimum Search Value” and “Lower N Limit” parameters are only required under the “Optimum” design criterion.)

The analysis results in a total sample size of 35, with 17 patients in stage one, and a further 18

added for stage two. The actual significance level is 0.028 and the power of the test is 85.01%. At the final analysis, if four or less responses are observed in total, then the drug is rejected. The overall probability of early termination is 41.8%.

**Step 3:**Once the calculation is completed, nQuery provides an output statement summarizing the results.

** It ****states:**

“Under the minimax design criterion, a sample size of 35 is required to test a null hypothesis of H₀: π ≤ 0.05 versus an alternative hypothesis of H₁: π ≥ 0.2 with a one-sided significance level of 0.028 and 85.01% power, where π is the true proportion of successes. This design results in an expected sample size of 27.474 and a probability of early termination of 0.418.

If the number of responses is less than or equal to 0 out of 17 subjects in the first stage then the trial will be stopped. If the trial proceeds to the second stage, 35 subjects in total will be studied. If 4 or less responses are observed, then the drug or treatment is rejected.”

**Step 4:**We can compare the Minimax design with the Optimum and Single Stage designs by completing two additional columns in nQuery with the same ⍺, 𝜋 0 , 𝜋 1 and power parameters and selecting the appropriate Design Criterion.

In this case, the optimum design results in a total sample size of 41, while the single-stage and

minimax designs result in a total sample size of 35.

**Step 5:**nQuery advanced also provides plotting options. To access the plotting tools, highlight the

completed columns that you wish to work with, go to the menu and select:

In this case, we will display how the total sample size for each design criterion is affected when

the maximum ineffective proportion varies between 0.005 and 0.075

The **Edit** button at the top of the output allows users to customize the appearance of the plot.

The null hypothesis (response = 5%) reflected a response rate of no clinical benefit while the

alternative hypothesis (response = 20%) reflected a desired response. The type 1 error (falsely

accepting a non-promising therapy) rate was set at 0.05 and the type II error (falsely rejecting a promising therapy) was set at 0.15. A two-stage design using a two-side type 1 error rate of

0.05 was conducted enrolling 17 evaluable participants in stage one and 18 participants in

stage two if one or more participants achieved a CR or PR

GraphPad Software DBA Statistical Solutions, 225 Franklin St FL 26 Boston, MA, 02110-2853, United States