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

Primary Purpose

Biliary Tract Cancer (BTC)

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Manganese Chloride

nab-paclitaxel

Gemcitabine

anti-PD-1 antibody

About this trial

This is an interventional treatment trial for Biliary Tract Cancer (BTC) focused on measuring local advanced, metastatic, anti-PD-1 antibody, Manganese, gemcitabine, cisplatin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 0-2.
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.

Sites / Locations

Biotherapeutic Department of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Manganese primed anti-PD-1 antibody plus nPG chemotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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

Secondary Outcome Measures

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.

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.

Overall survival (OS)

OS time was measured from the study entry to the date of death.

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.

Full Information

NCT ID

NCT04004234

First Posted

June 28, 2019

Last Updated

July 5, 2019

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04004234

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 1, 2019 (Actual)

Primary Completion Date

August 31, 2020 (Anticipated)

Study Completion Date

August 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Biliary Tract Cancer (BTC)

Keywords

local advanced, metastatic, anti-PD-1 antibody, Manganese, gemcitabine, cisplatin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Manganese primed anti-PD-1 antibody plus nPG chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Manganese Chloride

Intervention Description

Administered by inhalation at 0.2 or 0.4mg/kg/d once daily in a 3-week cycle

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

Paclitaxel For Injection (Albumin Bound)

Intervention Description

Administered intravenously, 125mg/m2/d on day1 and day8 in a 3-week cycle

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Administered intravenously, 1g/m2/d on day1 and day8 in a 3-week cycle

Intervention Type

Drug

Intervention Name(s)

anti-PD-1 antibody

Other Intervention Name(s)

Anti-PD-1 monoclonal antibody; PD-1 inhibitor

Intervention Description

Administered intravenously, 2-4mg/kg on day 3 in a 3-week cycle

Primary Outcome Measure Information:

Title

Number of Subjects with treatment-related adverse events (AEs)

Description

Time Frame

12 months

Title

Progression-free survival (PFS) at 6 months

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Disease control rate (DCR)

Description

Time Frame

12 months

Title

Object response rate (ORR)

Description

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.

Time Frame

12 months

Title

Overall survival (OS)

Description

OS time was measured from the study entry to the date of death.

Time Frame

24 months

Title

Number of participants with laboratory test abnormalities

Description

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.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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 0-2. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Weidong Han

Phone

86(10)66937463

hanwdrsw@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

Kaichao Feng

Phone

86(10)55499341

timothyfkc@126.com

Facility Information:

Facility Name

Biotherapeutic Department of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact: