A Phase I/II Study of the Pan-immunotherapy in Patients With Local Advanced/Metastatic BTC

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

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.

Study Overview

• Status: Unknown
• Conditions: Biliary Tract Cancer (BTC)
• Intervention / Treatment: Drug: Manganese Chloride; Drug: nab-paclitaxel; Drug: Gemcitabine; Drug: anti-PD-1 antibody

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital
      • Principal Investigator: Kaichao Feng, M.S
      • Principal Investigator: Yan Zhang, M.S
      • Principal Investigator: Meixia Chen, M.S
      • Sub-Investigator: Jiejie Liu, B.S
      • Sub-Investigator: Xiang Li, B.S
      • Sub-Investigator: Liang Dong, B.S

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥ 18 years old.
2. Life expectancy of at least 3 months.
3. Subjects must have Histopathological/cytological diagnosis of unresectable or recurrent /metastatic biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder).
4. Eastern Cooperative Oncology Group performance status 0-2.
5. Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
6. 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.
7. Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
8. Adequate organ function.
9. 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:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. Prior organ allograft.
4. Women who are pregnant or breastfeeding.
5. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Manganese Chloride; Administered by inhalation at 0.2 or 0.4mg/kg/d once daily in a 3-week cycle; Drug: nab-paclitaxel; Administered intravenously, 125mg/m2/d on day1 and day8 in a 3-week cycle; Other Names: Paclitaxel For Injection (Albumin Bound); Drug: Gemcitabine; Administered intravenously, 1g/m2/d on day1 and day8 in a 3-week cycle; Drug: anti-PD-1 antibody; Administered intravenously, 2-4mg/kg on day 3 in a 3-week cycle; Other Names: Anti-PD-1 monoclonal antibody; PD-1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Progression-free survival (PFS) at 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	6 months

Secondary Outcome Measures

Outcome Measure	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.	12 months
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
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

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): August 31, 2020
• Study Completion (Anticipated): August 31, 2021

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: July 5, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: cisplatin; metastatic; gemcitabine; anti-PD-1 antibody; local advanced; Manganese
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Trace Elements; Micronutrients; Gemcitabine; Paclitaxel; Antibodies; Immunoglobulins; Albumin-Bound Paclitaxel; Immune Checkpoint Inhibitors; Manganese
• Other Study ID Numbers: CHN-PLAGH-BT-042

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No