Epithelial ovarian cancer is the most lethal gynecologic malignancy, and most patients eventually relapse and develop resistance to available therapies. Immune checkpoint inhibitors have shown limited overall efficacy in recurrent ovarian cancer, partly because of its immunosuppressive tumor microenvironment. Manganese (Mn2+) can activate the cGAS-STING pathway and may enhance antitumor immunity and the therapeutic effects of PD-1 blockade combined with chemotherapy. Following encouraging findings from an early-phase study, a randomized, single-blind, placebo-controlled phase II trial showed that the addition of manganese chloride to anti-PD-1 antibody, nab-paclitaxel, and cisplatin improved clinical outcomes compared with placebo, with an overall manageable safety profile. Based on these findings, this phase III trial is designed to confirm the efficacy and further evaluate the safety of Mn2+-primed immunochemotherapy in patients with advanced ovarian cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Administered by inhalation at 0.4mg/kg twice per week in the first 3-week cycle, and then inhaled 0.4mg/kg twice in the first week of each 3-week cycle thereafter
Administered intravenously, 180-220mg/m2 on day 2 in a 3-week cycle (day 1 without Manganese priming)
Administered intravenously, Cisplatin (60-80mg/m2) or Carboplatin (area under the curve \[AUC\] 4-6 mg/ mL per min) on day 2 in a 3-week cycle (day 1 without Manganese priming)
Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming)
Administered by inhalation twice per week in the first 3-week cycle, and then inhaled twice in the first week of each 3-week cycle thereafter
Department of Obstetrics and Gynecology, Seventh Medical Center, Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGDepartment of Bio-therapeutic, First Medical Center, Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGDepartment of Obstetrics and Gynecology, First Medical Center, Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGPeking University International Hospital
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGDepartment of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital
Tangshan, Hebei, China
NOT_YET_RECRUITINGDepartment of Gynecologic Oncology, Shanxi Province Cancer Hospital
Taiyuan, Shanxi, China
NOT_YET_RECRUITINGProgression-free survival (PFS)
PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: 12 months
Overall survival (OS)
OS time was measured from the study entry to the date of death.
Time frame: 24 months
Object response rate (ORR)
ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to the RECIST V1.1.
Time frame: 24 months
Number of Subjects with treatment-related adverse events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.
Time frame: 12 months
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