Back to resultsAPG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
Primary Purpose
Advanced Pancreatic Cancer
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
APG-1387 for Injection
Gemcitabine
Nab paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Pancreatic Cancer focused on measuring IAP inhibitor, APG-1387, Pancreatic cancer, Inhibitor of apoptosis
Eligibility Criteria
Inclusion Criteria:
- Subjects must be ≥18 years of age at time of informed consent
- Able to comply with the study protocol, in the investigator's judgment
- Expected survival ≥ 3 months
Histology or cytology confirmed as advanced pancreatic adenocarcinoma, and:
- Standard treatment failed or intolerant to standard treatment(Phase Ib);
- First line standard treatment failed (Phase II).
- ECOG 0-1;
- Adequate organ function.
- Subjects must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment
Exclusion Criteria:
- Has had chemotherapy, radiation, target or other antitumor therapy within 14 days prior to the first dose of study drug.
- Has received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
- Has received a therapy with TNFα within 28 days of the first dose of study drug.
- Known active central nervous system involvement.
- Has received IAP-inhibitor before.
- Has had major surgery within 28 days of dosing of investigational agent, or minor surgery within 14 days.
- Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive, Human Immunodeficiency Virus (HIV) antibody positive.
- Pregnant or breastfeeding (lactating) women.
- Other situations that investigator think not suit for study.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
APG1387 in combination with Gemcitabine and Nab-Paclitaxel
Arm Description
Outcomes
Primary Outcome Measures
Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ).
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
Overall Response Rate (Applicable for: phase II stage) .
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Secondary Outcome Measures
Progression Free Survival (PFS)
From date of treatment start until the date of progression or the date of death due to any cause.
Duration of Response (DOR)
From date of response until the date of progression.
Overall Survival (OS)
From date of treatment start until the date of death due to any cause.
Maximum plasma concentration (Cmax)
Cmax of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Area under the plasma concentration versus time curve (AUC)
AUC of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Adverse events
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Full Information
NCT ID
NCT04643405
First Posted
November 19, 2020
Last Updated
September 7, 2023
Sponsor
Ascentage Pharma Group Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04643405
Brief Title
APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
Official Title
An Open Label, Multiple Centers Phase Ib/II Study of APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 17, 2021 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascentage Pharma Group Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a two stage study consisting of a dose escalation phase Ib and a phase II study which include subjects with previously-treated, advanced pancreatic adenocarcinoma. Dose Limiting Toxicities (DLTs) and maximum tolerated dose (MTD) of APG1387 in combination with nab-paclitaxel and gemcitabine will be evaluated in the dose escalation phase Ib. Safety and efficacy of APG1387 plus gemcitabine and nab-paclitaxel will be evaluated in phase II.
Detailed Description
The ability of tumor cells to evade apoptosis is currently a major problem in anti-tumor therapy. IAPs are an important class of apoptosis-regulating proteins. APG-1387, a potent bivalent SMAC mimetic, small molecule of IAP inhibitor, which could inhibit pancreatic cancer proliferation as monotherapy and in combination with chemotherapy through apoptosis pathway.
It's an open label, multiple centers phase Ib/II Study. Safety and tolerability of APG1387 combined with nab-paclitaxel and gemcitabine will be evaluated in phase Ib in previously-treated, advanced pancreatic adenocarcinoma patients. Efficacy and tolerability will be evaluated in phase II study in first line standard treatment failed metastatic pancreatic adenocarcinoma patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Pancreatic Cancer
Keywords
IAP inhibitor, APG-1387, Pancreatic cancer, Inhibitor of apoptosis
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
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
APG1387 in combination with Gemcitabine and Nab-Paclitaxel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
APG-1387 for Injection
Intervention Description
APG1387 will be administered IV days 1， 8, 15 and 22 of a 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine 1000 mg/m^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
Nab-Paclitaxel 125mg/m^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLT) of combination therapy (Applicable for: phase Ib stage ).
Description
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
Time Frame
28 days.
Title
Overall Response Rate (Applicable for: phase II stage) .
Description
Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Time Frame
Up to 2 years.
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
From date of treatment start until the date of progression or the date of death due to any cause.
Time Frame
Up to 2 years.
Title
Duration of Response (DOR)
Description
From date of response until the date of progression.
Time Frame
Up to 2 years.
Title
Overall Survival (OS)
Description
From date of treatment start until the date of death due to any cause.
Time Frame
Up to 2 years.
Title
Maximum plasma concentration (Cmax)
Description
Cmax of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Time Frame
28 days.
Title
Area under the plasma concentration versus time curve (AUC)
Description
AUC of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.
Time Frame
28 days.
Title
Adverse events
Description
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Time Frame
Up to 2 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must be ≥18 years of age at time of informed consent
Able to comply with the study protocol, in the investigator's judgment
Expected survival ≥ 3 months
Histology or cytology confirmed as advanced pancreatic adenocarcinoma, and:
Standard treatment failed or intolerant to standard treatment(Phase Ib);
First line standard treatment failed (Phase II).
ECOG 0-1;
Adequate organ function.
Subjects must have at least one measurable lesion evaluated by Computed Tomography (CT) scan on RECIST ver.1.1 at pre-treatment
Exclusion Criteria:
Has had chemotherapy, radiation, target or other antitumor therapy within 14 days prior to the first dose of study drug.
Has received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
Has received a therapy with TNFα within 28 days of the first dose of study drug.
Known active central nervous system involvement.
Has received IAP-inhibitor before.
Has had major surgery within 28 days of dosing of investigational agent, or minor surgery within 14 days.
Patients with clinically evident Hepatitis B surface antigen (HBs) positive, Hepatitis C virus (HCV) antibody positive, Human Immunodeficiency Virus (HIV) antibody positive.
Pregnant or breastfeeding (lactating) women.
Other situations that investigator think not suit for study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xianjun Yu, MD
Phone
+86-21-64175590
Email
yuxianjun@fudanpci.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yifan Zhai, MD, PhD
Organizational Affiliation
Jiangsu Ascentage Pharma Co., Ltd.
Official's Role
Study Chair
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Si Shi, PhD
Phone
+86-21-64175590
Email
shisi@fudanpci.org
12. IPD Sharing Statement
Learn more about this trial
APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma
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