Back to resultsThe Safety and Efficacy of Deferoxamine for Treating Unresectable Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma Non-resectable
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Conventional TACE
Deferoxamine and conventional TACE
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma Non-resectable focused on measuring Deferoxamine, Transarterial chemoembolization, Unresectable hepatocellular carcinoma
Eligibility Criteria
Inclusion Criteria:
- Adult patients, ≥ 18 years of age.
- The participant must have histologically-confirmed, unresectable HCC
- At least 1 measurable lesion, and overall tumor lesions occupying < 50% of liver volume
- The participant has provided signed informed consent
- No known allergy to contrast media
- Not pregnant
- No vascular anatomy or bleeding that would preclude catheter placement or emboli injection
Exclusion Criteria:
- Patients receiving concurrent radiotherapy or immunotherapy.
- Patients who have received previous chemotherapy, biological agents, or radiotherapy.
- Prior transarterial chemoembolisation (TACE) or transarterial embolisation (TAE).
- Prior liver transplantation or liver resection.
- Current or recent (within 10 days of study start) use of full-dose anticoagulants for therapeutic purposes.
- Patients with high risk esophageal/gastric varices.
- The participant has central nervous system (CNS) metastases or carcinomatous meningitis
- The participant has poorly-controlled hypertension [in other words (ie), blood pressure in abnormal range despite medical management]
Sites / Locations
- 960th hospital of PLARecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Deferoxamine
Conventional TACE
Arm Description
Patients are treated with deferoxamine and conventional TACE.
Patients are treated with conventional TACE.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer
PFS is defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who are alive and without disease progression and participants who did not progress and are subsequently lost to follow-up are censored at the last objective tumor assessment.
Secondary Outcome Measures
Time to Progression
The time from first day of therapy to the first date of objective evidence of progressive disease (PD) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is defined as having at least a 20% increase in sum of longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of new lesion. Time to PD is censored at the date of death or study discontinuation.
Overall Survival
Overall survival (OS) is the duration from first dose to death due to any cause. OS is censored at last contact date for participants who are alive at the end of follow-up period or lost to follow-up.
Percentage of Participants With Complete Response or Partial Response
Objective response rate (ORR) is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). As classified according to Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR is the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of non-target lesions. PR is having at least a 30% decrease in sum of longest diameter of target lesions.
Duration of Response
Duration of response is the interval from the date of initial documented response [complete response (CR) , partial response (PR) or Stable disease] to the first documented date of disease progression, initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR is the disappearance of all target lesions, PR is having at least a 30% decrease in the sum of the longest diameter of target lesions, and stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data are censored for participants who did not progress or die.
Tumor Necrosis
Tumor necrosis is quantified in liver lesions greater than 2 cm at Baseline. When MRI showed many cut surfaces for a single tumor, tumor size and the size of necrotic area is measured by accumulation of the serial sections containing the tumor. Lipiodol accumulation without contrast enhance in tumor after TACE is regarded as an indication of necrosis. Tumor necrosis is assessed at Baseline and 1-3 days prior to the next scheduled transarterial chemoembolisation (TACE) till disease progression. The extent of tumor necrosis is presented as the percentage of the tumor volume at Baseline.
Number of Participants With Iron Reduction of Liver
The iron of liver will be measured by MRI, where R2* and QSM is applied to present the quantity of iron. Iron reduction is assessed at Baseline and 1-3 days prior to the next scheduled transarterial chemoembolisation. The test will be repeated 1 -3 days after the therapy. The reduction of liver iron will be calculated accordingly.
The Prognostic Value of Reduction of Liver Iron
The iron of liver will be measured by MRI, where R2* and QSM is applied to present the quantity of iron. All patients will undergo MRI before TACE, and the test will be repeated 1 -3 days after the therapy till disease progression. The reduction of liver iron will be calculated accordingly. Based on the measurements mentioned above, the prognostic value of reduction of liver iron will be analyzed.
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that are considered by the investigator to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Full Information
NCT ID
NCT03652467
First Posted
August 22, 2018
Last Updated
February 20, 2019
Sponsor
Jinan Military General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03652467
Brief Title
The Safety and Efficacy of Deferoxamine for Treating Unresectable Hepatocellular Carcinoma
Official Title
The Safety and Efficacy of Deferoxamine Combined With Conventional Transarterial Chemoembolization in Patients With Unresectable Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jinan Military General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
To investigate the safety and efficacy of deferoxamine (DFO) combined with conventional transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC).
Detailed Description
DFO, an iron chelator, is considered as a potential drug to the treatment of HCC. Ferrum is an important transition metal for organisms and the liver plays a major role in its storage. However, in pathologic conditions, it will lead to hepatocyte injury through the free radicals generated by excess iron. In addition, excess iron accumulation in the liver increases toxic free iron, which is closely associated with hepatic inflammation, as well as the development and progression of HCC. Reduction of iron is likely an important therapeutic targets for treating HCC. Iron reduction therapy has been efficacious in both in animal HCC models and results of clinical studies also suggest potential efficacy for HCC. DFO chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions. The investigators assume that DFO, combined with TACE, may provide additional efficacy in patients with unresectable HCC.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma Non-resectable
Keywords
Deferoxamine, Transarterial chemoembolization, Unresectable hepatocellular carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Deferoxamine
Arm Type
Experimental
Arm Description
Patients are treated with deferoxamine and conventional TACE.
Arm Title
Conventional TACE
Arm Type
Active Comparator
Arm Description
Patients are treated with conventional TACE.
Intervention Type
Drug
Intervention Name(s)
Conventional TACE
Other Intervention Name(s)
TACE
Intervention Description
Conventional chemoembolization drugs are injected through hepatic artery.
Intervention Type
Drug
Intervention Name(s)
Deferoxamine and conventional TACE
Other Intervention Name(s)
Deferoxamine & TACE
Intervention Description
Deferoxamine is injected before conventional transarterial chemoembolization.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer
Description
PFS is defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who are alive and without disease progression and participants who did not progress and are subsequently lost to follow-up are censored at the last objective tumor assessment.
Time Frame
First dose to date of progressive disease or death due to any cause [every 3 cycles up to 36 months (1 cycle=2 weeks)]
Secondary Outcome Measure Information:
Title
Time to Progression
Description
The time from first day of therapy to the first date of objective evidence of progressive disease (PD) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is defined as having at least a 20% increase in sum of longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of new lesion. Time to PD is censored at the date of death or study discontinuation.
Time Frame
First dose to date of PD [every 3 cycles up to 36 months (1 cycle=2 weeks)]
Title
Overall Survival
Description
Overall survival (OS) is the duration from first dose to death due to any cause. OS is censored at last contact date for participants who are alive at the end of follow-up period or lost to follow-up.
Time Frame
First dose to date of death up to 36 months
Title
Percentage of Participants With Complete Response or Partial Response
Description
Objective response rate (ORR) is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR). As classified according to Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR is the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of non-target lesions. PR is having at least a 30% decrease in sum of longest diameter of target lesions.
Time Frame
First dose to date of objective progressive disease (PD) or death up to 36 months
Title
Duration of Response
Description
Duration of response is the interval from the date of initial documented response [complete response (CR) , partial response (PR) or Stable disease] to the first documented date of disease progression, initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, CR is the disappearance of all target lesions, PR is having at least a 30% decrease in the sum of the longest diameter of target lesions, and stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Disease progression is having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Data are censored for participants who did not progress or die.
Time Frame
Time of first response (CR, PR or Stable disease) to disease progression, or death due to any cause [every 3 cycles up to 36 months (1 cycle=2 weeks)]
Title
Tumor Necrosis
Description
Tumor necrosis is quantified in liver lesions greater than 2 cm at Baseline. When MRI showed many cut surfaces for a single tumor, tumor size and the size of necrotic area is measured by accumulation of the serial sections containing the tumor. Lipiodol accumulation without contrast enhance in tumor after TACE is regarded as an indication of necrosis. Tumor necrosis is assessed at Baseline and 1-3 days prior to the next scheduled transarterial chemoembolisation (TACE) till disease progression. The extent of tumor necrosis is presented as the percentage of the tumor volume at Baseline.
Time Frame
Baseline to the end of the study (up to 3 years, 36 months)
Title
Number of Participants With Iron Reduction of Liver
Description
The iron of liver will be measured by MRI, where R2* and QSM is applied to present the quantity of iron. Iron reduction is assessed at Baseline and 1-3 days prior to the next scheduled transarterial chemoembolisation. The test will be repeated 1 -3 days after the therapy. The reduction of liver iron will be calculated accordingly.
Time Frame
Baseline to the end of the study (up to 3 years, 36 months)
Title
The Prognostic Value of Reduction of Liver Iron
Description
The iron of liver will be measured by MRI, where R2* and QSM is applied to present the quantity of iron. All patients will undergo MRI before TACE, and the test will be repeated 1 -3 days after the therapy till disease progression. The reduction of liver iron will be calculated accordingly. Based on the measurements mentioned above, the prognostic value of reduction of liver iron will be analyzed.
Time Frame
Prior to TACE at baseline, 1 -3 days after the therapy
Title
Number of Participants With Drug-Related Treatment-Emergent Adverse Events
Description
Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that are considered by the investigator to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame
First dose to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients, ≥ 18 years of age.
The participant must have histologically-confirmed, unresectable HCC
At least 1 measurable lesion, and overall tumor lesions occupying < 50% of liver volume
The participant has provided signed informed consent
No known allergy to contrast media
Not pregnant
No vascular anatomy or bleeding that would preclude catheter placement or emboli injection
Exclusion Criteria:
Patients receiving concurrent radiotherapy or immunotherapy.
Patients who have received previous chemotherapy, biological agents, or radiotherapy.
Prior transarterial chemoembolisation (TACE) or transarterial embolisation (TAE).
Prior liver transplantation or liver resection.
Current or recent (within 10 days of study start) use of full-dose anticoagulants for therapeutic purposes.
Patients with high risk esophageal/gastric varices.
The participant has central nervous system (CNS) metastases or carcinomatous meningitis
The participant has poorly-controlled hypertension [in other words (ie), blood pressure in abnormal range despite medical management]
Facility Information:
Facility Name
960th hospital of PLA
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250031
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Li, M.D.
Phone
13953176057
Email
liminyingxiang@163.com
12. IPD Sharing Statement
Learn more about this trial
The Safety and Efficacy of Deferoxamine for Treating Unresectable Hepatocellular Carcinoma
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