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Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Platinum chemotherapy has been widely adopted as a standard treatment for advanced ovarian cancer, the response rates in patients with relapsed/refractory ovarian cancer is unacceptably low. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This two-arm, phase I/II study is designed to assess the safety and efficacy of combined therapy of anti-PD-1 antibody and chemotherapy with or without Manganese priming.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Manganese primed Sintilimab plus nPP chemotherapy | Experimental | Subject received Manganese primed Sintilimab, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent. |
|
| Sintilimab plus nPP chemotherapy | Active Comparator | Subject received Sintilimab, nab-paclitaxel and platinum chemotherapy every 3 weeks until achieving a second assessable complete response or progressive disease, development of unacceptable toxicity, or withdrawal of consent. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Object response rate (ORR) | ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 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. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Disease control rate (DCR) | DCR is defined as the proportion of subjects who achieved a stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 12 months |
| Progression-free survival (PFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department of Chinese PLA General Hospital | Beijing | Beijing Municipality | 100853 | China |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
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| ID | Term |
|---|---|
| C025340 | manganese chloride |
| C520255 | 130-nm albumin-bound paclitaxel |
| D017239 | Paclitaxel |
| D007267 | Injections |
| C000632826 | sintilimab |
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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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) |
|
|
| 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) |
|
| Sintilimab | Drug | Administered intravenously, 200mg on day 3 in a 3-week cycle (day 2 without Manganese priming) |
|
|
PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1. |
| 12 months |
| Overall survival (OS) | OS time was measured from the study entry to the date of death. | 24 months |
| Number of participants with laboratory test abnormalities | The laboratory tests of serum cytokines and chemokines will be performed on day 1 and 3 of each cycle, and the abnormality will be determined by the investigator. | 12 months |
| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |