A Randomized, Single-blind, Placebo-controlled, Phase 2 Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Relapsed/Refractory Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- Manganese Chloride
- Conditions
- Ovarian Cancer
- Sponsor
- Chinese PLA General Hospital
- Enrollment
- 84
- Locations
- 1
- Primary Endpoint
- Object response rate (ORR)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Han weidong
Professor
Chinese PLA General Hospital
Eligibility Criteria
Inclusion Criteria
- •Subjects must have histologically proven relapsed or refractory ovarian cancer (Refractory was defined as a lack of response to or progression during the frontline treatment; relapsed was defined as progression after the frontline treatment), including patients diagnosed with primary carcinoma of fallopian tube or peritoneum carcinoma.
- •≥ 18 years old.
- •Life expectancy of at least 6 months.
- •Eastern Cooperative Oncology Group performance status 0-
- •Radiographic imaging (CT/MRI/PET-CT) indicated recurrence or metastasis; or cancer cells in ascites are positive; or CA125 concentration in the peripheral blood is more than 2 times the upper limit of normal value.
- •Subjects must have received at least two frontline therapies, at least one of which is platinum-containing.
- •Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
- •Adequate organ function.
- •Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
Exclusion Criteria
- •Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- •Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
- •Prior organ allograft.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- •Subjects with previous or concurrent other malignancies.
Arms & Interventions
Manganese primed Sintilimab plus nPP chemotherapy
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.
Intervention: Manganese Chloride
Manganese primed Sintilimab plus nPP chemotherapy
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.
Intervention: nab-paclitaxel
Manganese primed Sintilimab plus nPP chemotherapy
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.
Intervention: Platinum chemotherapy
Manganese primed Sintilimab plus nPP chemotherapy
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.
Intervention: Sintilimab
Sintilimab plus nPP chemotherapy
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.
Intervention: nab-paclitaxel
Sintilimab plus nPP chemotherapy
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.
Intervention: Platinum chemotherapy
Sintilimab plus nPP chemotherapy
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.
Intervention: Sintilimab
Outcomes
Primary Outcomes
Object response rate (ORR)
Time Frame: 24 months
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
Number of Subjects with treatment-related adverse events (AEs)
Time Frame: 12 months
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.
Secondary Outcomes
- Disease control rate (DCR)(12 months)
- Progression-free survival (PFS)(12 months)
- Overall survival (OS)(24 months)
- Number of participants with laboratory test abnormalities(12 months)