- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04612712
A Phase 1/2 Study of Donafenib in Combination With KN046 in Advanced Gastrointestinal Tumors
November 28, 2022 updated by: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
A Phase 1/2 Dose Escalation and Expansion Study of Donafenib Tosilate Tablets in Combination With KN046 Injection in Advanced Gastrointestinal Tumors
This study is an open, multi-center clinical trial, the purpose is to study the safety and preliminary efficacy of Donafenib combined with KN046 in subjects with Advanced Gastrointestinal Tumors.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
The study consists of dose escalation and dose expansion.
The preset dose of Donafenib is 50 mg BID, 100 mg BID and 200 mg BID, and the preset dose of KN046 is 5 mg/kg Q3W.
Dose expansion will enroll subjects who with advanced hepatocellular carcinoma.
Study Type
Interventional
Enrollment (Anticipated)
42
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Tianshu Liu, PhD
- Phone Number: 021-64041990
- Email: Liu.tianshu@zs-hospital.sh.cn
Study Locations
-
-
-
Shanghai, China
- Recruiting
- Zhongshan Hospital affiliated to Fudan University
-
Contact:
- Tianshu Liu
- Phone Number: 02164041990
- Email: Liu.tianshu@zs-hospital.sh.cn
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female aged 18-70 years;
- Phase I dose escalation: Advanced gastric cancer, esophageal cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer (other than pancreatic neuroendocrine tumors) and intrahepatic cholangiocarcinoma that failed standard treatments confirmed by histopathology and/or cytology; Among them, the Child-Pugh score of liver function in patients with hepatocellular carcinoma is less than 5,
- Phase II advanced hepatocellular carcinoma Dose expansion: Patients with advanced hepatocellular carcinoma who are clinically diagnosed or confirmed by histopathology and/or cytology and are not suitable for surgical resection; The patient has not undergone first-line systemic treatment [small molecule targeted drugs (such as sorafenib, lenvatinib, etc.), systemic chemotherapy] and tumor immunotherapy (anti-PD-1/L1, CTLA-4, etc.); Child-Pugh score of liver function ≤ 6;
- Has at least one measurable lesion based on RECIST 1.1;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- Life expectancy ≥12 weeks;
- Patients must be able to understand and willing to sign a written informed consent document.
Exclusion Criteria:
- Subjects who have previously received immune checkpoint inhibitors (such as anti-PD-1/L1, CTLA-4, etc.);
- History of interstitial lung disease or non-infectious pneumonia;
- Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients undergoing total gastrectomy;
- Has received vaccination within 4 weeks prior to the first dose.
- Has participated in other anticancer drug clinical trials within 4 weeks.
- According to the judgement of the investigators, there are other factors that subjects are not suitable for the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Donafenib+ KN046
Donafenib 50mg BID/100 mg BID/200 mg BID orally + KN046 5mg/kg Q3W iv
|
In the dose exploration phase (phase I) : three doses of Donafenib tosylate tablets [50 mg twice a day; 100 mg twice a day; 200 mg twice a day ] will be explored.
In the dose expansion phase (phase II), patients with advanced hepatocellular carcinoma will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the dose escalation study.
5mg/kg Q3W
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I part - Tolerability of Donafenib in Combination With KN046
Time Frame: 21 days after the first dose of Donafenib and KN046
|
Evaluated by severity of drug-related adverse events (AEs), serious adverse events (SAEs).
|
21 days after the first dose of Donafenib and KN046
|
Phase II part - Objective response rate(ORR)
Time Frame: From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 36 months]
|
Objective response rate based on the RECIST 1.1 by investigator.
Percentage of subjects achieving complete response (CR) and partial response (PR).
|
From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 36 months]
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of Response (DOR)
Time Frame: Through study completion, an expected average of 3 year
|
It is defined as time between the date of first radiographic documented objective response and the date of the radiographic documented disease progression.
|
Through study completion, an expected average of 3 year
|
Progression-Free Survival (PFS)
Time Frame: Through study completion, an expected average of 3 year
|
PFS is defined as the time from date of enrollment to the date of the first objectively documented tumor progression or death due to any cause.
|
Through study completion, an expected average of 3 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Chair: Tianshu Liu, PhD, Shanghai Zhongshan Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
January 19, 2021
Primary Completion (ANTICIPATED)
December 1, 2023
Study Completion (ANTICIPATED)
December 1, 2023
Study Registration Dates
First Submitted
October 29, 2020
First Submitted That Met QC Criteria
October 29, 2020
First Posted (ACTUAL)
November 3, 2020
Study Record Updates
Last Update Posted (ACTUAL)
November 29, 2022
Last Update Submitted That Met QC Criteria
November 28, 2022
Last Verified
November 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KN046D-C-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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