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

Biliary Tract Cancer (BTC) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04004234
• Other study ID #: CHN-PLAGH-BT-042
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2019
• Est. completion date: August 31, 2021

Study information

• Verified date: July 2019
• Source: Chinese PLA General Hospital
• Contact: Weidong Han
• Phone: 86(10)66937463
• Email: hanwdrsw[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 31, 2021
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Cancer (BTC)
• Biliary Tract Neoplasms

Intervention

Drug:
• Manganese Chloride
Administered by inhalation at 0.2 or 0.4mg/kg/d once daily in a 3-week cycle
• nab-paclitaxel
Administered intravenously, 125mg/m2/d on day1 and day8 in a 3-week cycle
• Gemcitabine
Administered intravenously, 1g/m2/d on day1 and day8 in a 3-week cycle
• anti-PD-1 antibody
Administered intravenously, 2-4mg/kg on day 3 in a 3-week cycle

Locations

Country	Name	City	State
China	Biotherapeutic Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Overall survival (OS)	OS time was measured from the study entry to the date of death.	24 months
Secondary	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