An Open-label, Phase I/II Study of the Pan-immunotherapy in Patients With Local Advanced/Metastatic Pancreatic Cancer

Phase 1

• Conditions: Pancreatic Cancer
• Interventions: Drug: Manganese Chloride; Drug: nab-paclitaxel; Drug: Gemcitabine; Drug: anti-PD-1 antibody

• Registration Number: NCT03989310
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

The outcome of pancreatic cancer is extremely poor. NCCN guidelines recommend FOLFIRINOX or modified-FOLFIRINOX as the first-line chemotherapeutic regimen, but the response rate 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 one-arm, phase I/II study is designed to assess the safety and efficacy of Manganese primed combined therapy of anti-PD-1 antibody and chemotherapy.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-03-01
• Study First Submitted: 2019-06-15
• Study First Submitted QC: 2019-06-15
• Study First Posted: 2019-06-18
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-20
• Last Update Posted: 2020-12-23
• Primary Completion: 2021-05-31
• Study Completion: 2022-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Subjects must have histologically proven local advanced/metastatic pancreatic cancer
2. ≥ 18 years old.
3. Life expectancy of at least 6 months.
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 with Anti-PD-1 antibody treatment history are eligible which must be resistance.
7. Adequate organ function.
8. 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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Manganese primed anti-PD-1 antibody plus nPG chemotherapy	Manganese Chloride	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.
anti-PD-1 antibody plus nPG chemotherapy	nab-paclitaxel	Subject received 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.
Manganese primed anti-PD-1 antibody plus nPG chemotherapy	nab-paclitaxel	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.
Manganese primed anti-PD-1 antibody plus nPG chemotherapy	anti-PD-1 antibody	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.
anti-PD-1 antibody plus nPG chemotherapy	anti-PD-1 antibody	Subject received 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.
Manganese primed anti-PD-1 antibody plus nPG chemotherapy	Gemcitabine	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.
anti-PD-1 antibody plus nPG chemotherapy	Gemcitabine	Subject received 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.

Primary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	12 months	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.
Number of Subjects with treatment-related adverse events (AEs)	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 Outcome Measures

Name	Time	Method
Object response rate (ORR)	12 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.
Progression-free survival (PFS)	12 months	PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1.
Overall survival (OS)	24 months	OS time was measured from the study entry to the date of death.
Number of participants with laboratory test abnormalities	12 months	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.

Trial Locations

Locations (1)

Biotherapeutic Department of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China