A Phase I/II, Open-label, Single-center Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Local Advanced/Metastatic Biliary Tract Cancer
Overview
- Phase
- Phase 1
- Intervention
- Manganese Chloride
- Conditions
- Biliary Tract Cancer (BTC)
- Sponsor
- Chinese PLA General Hospital
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS) at 6 months
- Last Updated
- 6 years ago
Overview
Brief Summary
Biliary tract cancer (BTC) is a rare heterogeneous collection of malignancies arising within the biliary tract, characterized by innate chemoresistance and abysmal prognosis. 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 open-label, phase I/II study is designed to assess the safety and efficacy of Manganese primed combined therapy of anti-PD-1 antibody and gemcitabine/cisplatin chemotherapy.
Investigators
Han weidong
Principal Investigator
Chinese PLA General Hospital
Eligibility Criteria
Inclusion Criteria
- •≥ 18 years old.
- •Life expectancy of at least 3 months.
- •Subjects must have Histopathological/cytological diagnosis of unresectable or recurrent /metastatic biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder).
- •Eastern Cooperative Oncology Group performance status 0-
- •Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
- •Subjects may have received prior radiotherapy, chemotherapy, or other local ablative therapies, which completed ≥ 4 weeks prior to registration AND patient has recovered to \<= grade 1 toxicity.
- •Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
- •Adequate organ function.
- •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.
Arms & Interventions
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
Intervention: Manganese Chloride
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
Intervention: nab-paclitaxel
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
Intervention: Gemcitabine
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
Intervention: anti-PD-1 antibody
Outcomes
Primary Outcomes
Progression-free survival (PFS) at 6 months
Time Frame: 6 months
Progression free survival (PFS) at 6 months in patients with local advanced /metastatic BTCs treated with the combined regimen. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (RECIST V1.1) definition
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)
- Overall survival (OS)(24 months)
- Object response rate (ORR)(12 months)
- Number of participants with laboratory test abnormalities(12 months)