A Phase 3 Study of Manganese-primed Immunochemotherapy in Patients With Advanced Ovarian Cancer
Sponsor: Chinese PLA General Hospital • ClinicalTrials.gov ID: NCT07822646
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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.
Interventions
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Manganese Chloride
(Drug)
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
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Nab-paclitaxel
(Drug)
Administered intravenously, 180-220mg/m2 on day 2 in a 3-week cycle (day 1 without Manganese priming)
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Platinum chemotherapy
(Drug)
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)
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Anti-PD-1 antibody
(Drug)
Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming)
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Placebo
(Drug)
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
Eligibility criteria
Conditions
Locations
- Department of Obstetrics and Gynecology, Seventh Medical Center, Chinese PLA General Hospital — Beijing, Beijing Municipality, China
- Department of Bio-therapeutic, First Medical Center, Chinese PLA General Hospital — Beijing, Beijing Municipality, China
- Department of Obstetrics and Gynecology, First Medical Center, Chinese PLA General Hospital — Beijing, Beijing Municipality, China
- Peking University International Hospital — Beijing, Beijing Municipality, China
- Department of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital — Tangshan, Hebei, China
- Department of Gynecologic Oncology, Shanxi Province Cancer Hospital — Taiyuan, Shanxi, China
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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
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