A Single-Center, Open-Label, Single-Arm, Phase I Study With Dose Expansion Cohort of Sacituzumab Govitecan in Combination With Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer
Summary
This is an open-label, Phase 1 study with a dose expansion cohort of Sacituzumab Govitecan in Combination with Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer. The goal of the study is to determine the optimal dose of sacituzumab govitecan for use in combination with cisplatin for treatment of epithelial ovarian and endometrial cancers.
Detailed description
This is an open-label, Phase 1 study with a dose expansion cohort (DEC), conducted in two separate disease groups (ovarian and endometrial cancer). The primary objective of the study is to determine the optimal dose of sacituzumab govitecan for use in combination with cisplatin for treatment of epithelial ovarian and endometrial cancers. For each disease group, there will be a safety run-in phase utilizing a 3+3 design with a de-escalated dose level if the starting dose shows toxicity and an expansion cohort to evaluate the preliminary efficacy and tolerability of the experimental regimen. The dose expansion cohort will consist of 14 patients in the ovarian cohort and 12 patients in the endometrial cohort with an additional 2 patients in each cohort to account for potential patient replacement. This will yield a total sample size of 22-28 patients in the ovarian cancer cohort and a total sample size of 20-26 patients in the endometrial cancer cohort. Phase 1, Safety Run-in with Dose De-escalation Scheme: Dose Level 0, starting level: Sacituzumab govitecan 7.5 mg/kg + Cisplatin 70 mg/m2 IV Dose -1: Sacituzumab govitecan 7.5 mg/kg + Cisplatin 70 mg/m2 IV In this stage, a minimum of 6 patients and a maximum of 12 patients will be required. The recommended dose expansion cohort (DEC) dose is defined as the highest dose at which no more than 1 out of 6 patients experience a Dose-Limiting Toxicity (DLT) Phase 2, Dose Expansion Cohort: Sacituzumab govitecan 5-7.5 mg/kg IV (depending on phase I result) + Cisplatin 70 mg/m2 IV. Drug product administration will continue until progressive disease (PD), unacceptable toxicity, or death. The primary endpoint of the safety run-in phase is to determine the recommended DEC dose of Sacituzumab in combination with a fixed schedule of cisplatin in patients with ovarian and endometrial cancers. In the safety run-in phase, the assessment of dose limiting toxicity (DLT) will be performed standard 3 + 3 design rules. The recommended DEC dose is defined as the highest dose of Sacituzumab in combination with Cisplatin at the fixed dose of 70 mg/m2 at which no more than 1 out of 6 patients experience DLT within the first cycle of therapy. The DEC is designed to indicate proof of concept regarding the overall response rate (ORR) and safety of the combination of sacituzumab with cisplatin at the dose established in the safety run-in phase of the study. Once the recommended DEC dose for sacituzumab and cisplatin combination has been established for each disease cohort, an additional 14 patients will be enrolled for the ovarian group and 12 patients for the endometrial group. An additional 2 patients will be added to each cohort to account for potential patient replacement for a total of 42-54 evaluable patients.
Arms & interventions
- DrugSacituzumab
Dose 0: Sacituzumab govitecan 7.5 mg/kg Dose -1: Sacituzumab govitecan 5 mg/kg
- DrugCisplatin
Cisplatin 70 mg/m2 IV
Outcome measures
Primary
Dose-limiting toxicity (DLT) at the maximum tolerated dose (MTD) for the Safety Run-In Phase
Safety Run-In Phase: The primary endpoint of the safety run-in phase is to determine DLT and the recommended DEC dose of sacituzumab govitecan in combination with a fixed schedule of cisplatin in patients with ovarian and endometrial cancers. DLT is defined as any therapy-attributable adverse event (AE) requiring discontinuation of therapy within one cycle of combined therapy; specifically grade 3 or 4 non-hematologic toxicity and grade 4 hematologic toxicity events. These will be assessed via NCI's CTCAE v 5.0 toxicity criteria. DEC dose is defined as the highest dose at which no more than 1 out of 6 patients experience a DLT. All primary endpoints will be reported separately for each of the ovarian and endometrial cohorts.
Time frame: within the first cycle of therapy (each cycle = 21 days)
Dose limiting toxicity (DLT) for the DEC Phase
A primary endpoint for the dose expansion cohort (DEC) phase of this study will be the DLT rate evaluated within 1 cycle of sacituzumab in combination with cisplatin. The DLT rate is defined as the proportion of patients in the safety population of the phase 1 and dose expansion cohort (DEC) phase of the study that experience at least 1 DLT within the first cycle of sacituzumab in combination with cisplatin treated at the maximum tolerated dose (MTD). DLT is defined as any therapy-attributable adverse event (AE) requiring discontinuation of therapy within one cycle of combined therapy; specifically grade 3 or 4 non-hematologic toxicity and grade 4 hematologic toxicity events. These will be assessed via NCI's CTCAE v 5.0 toxicity criteria. All primary endpoints will be reported separately for each of the ovarian and endometrial cohorts.
Time frame: within 1 cycle of therapy (each cycle = 21 days)
Overall Response Rate (ORR)
A primary endpoint for the dose expansion cohort (DEC) phase will be the ORR evaluated within 3 cycles of sacituzumab in combination with cisplatin in patients with platinum-sensitive recurrent epithelial ovarian cancer and endometrial cancer. This will be measured every 3 cycles (12 weeks +/- 1 week). The overall response rate is defined as the proportion of patients in the full analysis (FA) population treated at the MTD, in both the phase 1 and DEC phases of the study, whose cancer decreases in size on assessment (as measured by the sum of complete response (CR) and partial response (PR)). Disease status will be assessed based on RECIST 1.1 criteria for measurable and non-measurable disease. The Full Analysis (FA) population includes all patients who received at least one cycle of all study medications and had at least one valid post-baseline efficacy assessment. All primary endpoints will be reported separately for each of the ovarian and endometrial cohorts.
Time frame: every 3 cycles (each cycle is 21 days)
Secondary
Clinical Benefit Response (CBR)
Time frame: 6 months
Progression free survival (PFS)
Time frame: 6 months
Number of adverse events
Time frame: 6 months
Eligibility criteria
Study locations (1)
Icahn School of Medicine at Mount Sinai Division of Hematology and Medical Oncology
New York, New York, 10029