Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

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Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Recurrence

Uterine Neoplasms

Endometrial Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Sacituzumab govitecan

Cisplatin

Immunoconjugates

Immunologic Factors

DEC 3+3 dose expansion of Sacituzumab Govitecan in Combination with Cisplatin

Dose 0: Sacituzumab govitecan 10 mg/kg

Dose 1: Sacituzumab govitecan 7.5 mg/kg

Sacituzumab

Amy Tiersten, MD

Melanie Kier, MD

Amy Tiersten

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.

This is an open-label, Phase 1 study with a dose expansion cohort, 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 10 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 7.5-10 mg/kg IV (depending on phase I result) + Cisplatin 70 mg/m2 IV.

Drug product administration will continue until PD, unacceptable toxicity, or death.

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 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.

Sacituzumab Govitecan in Combination With Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer

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

There are no plans to share individual participant data, supporting information, or biological samples that are collected as part of this study for future research, even if the participant's identity is removed. Data and samples will only be used to complete this study. If the results of this study are presented or reported in a publication, the participants will not be identified. All results will be kept confidential and will not be divulged without permission, except as required by law.

Safety Run-In Phase: Dose-limiting toxicity (DLT) and the recommended Dose Expansion Cohort (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.

Dose Expansion Cohort Phase: 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. The DLT rate for the DEC cohort is define as the proportion of patients in the safety population and 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)

Overall Response Rate

ORR will be measured by the percentage of patients whose cancer decreases in size on assessment. This will be measured as the sum of complete response and partial response by RECISIT 1.1 criteria.

CBR will be measured by the percentage of patients whose cancer shrinks or remains stable over the duration of the study. This will be measured as the sum of complete response (CR), partial response (PR), and stable disease (SD) for greater than or equal to 6 months.

6 month progression free survival (PFS) as defined as the time from the start of treatment until confirmed disease progression or death from any cause, whichever occurs first. Disease status (i.e., SD, PR, PR, CR or progressive disease (PD)) will be assessed based on RECIST 1.1 criteria for measurable and non-measurable disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sacituzumab Govitecan in Combination With Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer	NCT06040970	Ovarian Cancer Malignant Neopl...	Sacituzumab Cisplatin	18 Years -	Icahn School of Medicine at Mount Sinai
Sacituzumab Govitecan in Combination With Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer	NCT06040970	Ovarian Cancer Malignant Neopl...	Sacituzumab Cisplatin	18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for malignant neoplasm of uterus