Patients will undergo a screening period of up to 4 weeks. Patients who are deemed eligible will be entered into the study and undergo treatment with G-202. G-202 will be administered by intravenous infusion over one hour on Days 1, 2 and 3 of a 28-day treatment cycle. The G-202 dose will be 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3.
The primary objective of the study is to determine the percentage of patients with chemotherapy-naïve metastatic castrate-resistant prostate cancer who do not have disease progression (radiographic or clinical) after 24 weeks of treatment with G-202.
A two-stage study design will be used to evaluate the percentage of patients who do not have disease progression after 24 weeks of treatment with G-202. If the percent of patients who are progression-free at 24 weeks is at most 15%, then the clinical efficacy of G-202 in this patient population will be considered unacceptably low. If, on the other hand, the percent of patients who are progression-free at 24 weeks is at least 35%, this will be considered sufficient evidence to consider further clinical investigation. The null hypothesis that the percent of patients who are progression-free at 24 weeks is at most 15% will be tested against the alternative hypothesis that the percent is greater than 15% at the one-sided 10% significance level. In order to avoid a suspension in accrual awaiting interim analysis, a two-stage study design for evaluating survival probabilities with continual accrual will be used.
An interim analysis for futility will be conducted after 24 evaluable patients have been accrued assuming that the time between accrual of the first patient and accrual of the 24th patient is at least 8 months. If 24 patients are accrued in less than 8 months, accrual will continue until the time period between the date of accrual of the first patient and the date of accrual of the last patient is at least 8 months. If the trial is not terminated for futility after the interim analysis, an additional 10 patients will be accrued for a total of 34 patients. The two-stage design minimizes the expected duration of accrual under the null hypothesis.
For the interim analysis, any patient who discontinues participation for reasons other than safety or disease progression before completing three full cycles and undergoing the 12-week follow-up assessment will be replaced. Any replaced patient will be included in all study analyses of the intent-to-treat and safety populations.
Safety will be assessed by the reporting of adverse events, vital signs and assessment of findings on physical exam and routine laboratory determinations. The severity of adverse events and laboratory findings will be assessed according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4.
