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The Safety and Efficacy of Deferoxamine for Treating Unresectable Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03652467
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : February 22, 2019
Sponsor:
Information provided by (Responsible Party):
Li Min, Jinan Military General Hospital

Brief Summary:
To investigate the safety and efficacy of deferoxamine (DFO) combined with conventional transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC).

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Non-resectable Drug: Conventional TACE Drug: Deferoxamine and conventional TACE Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Safety and Efficacy of Deferoxamine Combined With Conventional Transarterial Chemoembolization in Patients With Unresectable Hepatocellular Carcinoma
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Deferoxamine
Patients are treated with deferoxamine and conventional TACE.
Drug: Deferoxamine and conventional TACE
Deferoxamine is injected before conventional transarterial chemoembolization.
Other Name: Deferoxamine & TACE

Active Comparator: Conventional TACE
Patients are treated with conventional TACE.
Drug: Conventional TACE
Conventional chemoembolization drugs are injected through hepatic artery.
Other Name: TACE




Primary Outcome Measures :
  1. Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer [ 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)] ]
    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 :
  1. Time to Progression [ Time Frame: First dose to date of PD [every 3 cycles up to 36 months (1 cycle=2 weeks)] ]
    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.

  2. Overall Survival [ Time Frame: First dose to date of death up to 36 months ]
    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.

  3. Percentage of Participants With Complete Response or Partial Response [ Time Frame: First dose to date of objective progressive disease (PD) or death up to 36 months ]
    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.

  4. Duration of Response [ 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)] ]
    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.

  5. Tumor Necrosis [ Time Frame: Baseline to the end of the study (up to 3 years, 36 months) ]
    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.

  6. Number of Participants With Iron Reduction of Liver [ Time Frame: Baseline to the end of the study (up to 3 years, 36 months) ]
    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.

  7. The Prognostic Value of Reduction of Liver Iron [ Time Frame: Prior to TACE at baseline, 1 -3 days after the therapy ]
    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.

  8. Number of Participants With Drug-Related Treatment-Emergent Adverse Events [ Time Frame: First dose to 36 months ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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]

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652467


Locations
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China, Shandong
960th hospital of PLA Recruiting
Jinan, Shandong, China, 250031
Contact: Min Li, M.D.    13953176057    liminyingxiang@163.com   
Sponsors and Collaborators
Jinan Military General Hospital

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Responsible Party: Li Min, Director, Jinan Military General Hospital
ClinicalTrials.gov Identifier: NCT03652467    
Other Study ID Numbers: JNZY20181245
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: February 2019

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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
Keywords provided by Li Min, Jinan Military General Hospital:
Deferoxamine
Transarterial chemoembolization
Unresectable hepatocellular carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Chlorotrianisene
Deferoxamine
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action