Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in HCC Patients With GALNT14-rs9679162-non-TT Genotype

May 4, 2021 updated by: Chau-ting, Yeh, Chang Gung Memorial Hospital

Randomized, Controlled, Open Label, Clinical Trial for Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in Hepatocellular Carcinoma Patients With GALNT14-rs9679162-non-TT Genotype

TACE against HCC is the standard of care for BCLC stage B patients. In this exploratory study, the investigators assess the efficacy of TACE with or without adagloxad simolenin/OBI-821 treatment in GALNT14 "non-TT" HCC population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Hepatocellular carcinoma (HCC) is the fifth most common solid cancers worldwide and the third leading cause of cancer-related death. Early stage HCC can be cured by surgical removal or non-surgical ablation procedures, albeit a high recurrence rate up to 75% in 5 years remains an unsolved problem. On the other hand, in patients with unresectable HCC, the "standard therapy" is still under intensive clinical investigations. In patients without portal vein occlusion/thrombosis or extrahepatic metastasis, namely Barcelona Clinical Liver Cancer (BCLC) Stage B, transcatheter arterial chemoembolization (TACE) is believed to be an effective palliative treatment. The beneficial effect of TACE on overall survival has been mild to moderate as reviewed in a previous study. Thus, TACE is generally considered a "palliative" therapy. TACE induces tumor necrosis but at the same time, it also induces angiogenesis owing to the increases of hypoxia-inducible factors and endothelial growth factors to trigger regrowth of tumors.

It has been known that GALNT14 genotype is associated with treatment responses. Patients with GALNT14 "TT" genotype response well to both TACE and chemotherapy.

A new immunotherapy is directed against Globo H, a carbohydrate antigen that is expressed at high levels on the surface of a variety of tumor cells. These Globo H-specific antibodies can effectively induce complement dependent cytotoxicity (CDC) as well as antibody-dependent cell-mediated cytotoxicity (ADCC) by IgM and IgG, respectively, together with other cellular immune responses to kill tumors. In the clinical setting, Globo H has been evaluated as the target of active immunotherapy in a few clinical trials including an ongoing Phase II/III trial of adagloxad simolenin/OBI-821 sponsored by OBI Pharma, Inc., as a potential treatment for stage IV metastatic breast cancers and possibly other cancer types expressing Globo series TACAs. Although vaccination with adagloxad simolenin/OBI-821 did not improve progression-free survival (PFS) in patients with previously treated metastatic breast cancer, in a post-hoc analysis, patients who developed a humoral immune response to Globo H had a longer PFS than those who did not, indicating that adagloxad simolenin/OBI-821 treatment could be of benefit when an antibody response can be developed.

Furthermore, overexpression of tumor-specific antigen Globo H can contribute to enhanced tumor angiogenesis and tumor-associated immune suppression, and in turn, positively correlate with tumor aggressiveness and poor survival in patients. In the present study, only "non-TT" (less favorable) groups will be enrolled and the patients will be randomized to examine the hypothesis that the TACE + adagloxad simolenin/OBI-821 treatment is beneficial in the BCLC class B, advanced HCC patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
    • Taoyuan
      • Taoyuan City, Taoyuan, Taiwan, 333
        • Linkou Chang Gung Memorial Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed Diagnosis of HCC
  2. Has a Globo-H or SSEA-3 positive tumor as determined by IHC
  3. Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.
  4. Patients should be in BCLC clinical stage B (multinodular asymptomatic tumors without extra-hepatic spread or portal vein invasion) with or without unilateral secondary or tertiary branches of portal vein invasion.
  5. Child-Pugh functional class A or B.
  6. GALNT14- rs9679162 "non TT" genotype
  7. At least 1 measurable lesion must be present.
  8. ECOG performance status 0 to 1.
  9. Age > 20 years
  10. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial and 4 weeks after last treatment
  11. Informed consent must be obtained prior to perform any study procedure.
  12. Total bilirubin < 3.0 mg/dL with no evidence of biliary tract obstruction.
  13. Appropriate Serum alanine aminotransferase, aspartate aminotransferase, Absolute neutrophil count, Platelets and Serum creatinine

(16) Antiviral treatment for hepatitis B or C is allowed except for interferon.

Exclusion Criteria:

  1. BCLC stage A.
  2. Presence of extrahepatic metastasis or main portal vein thrombosis.
  3. Child-Pugh score = C.
  4. Significant cardiac disease as determined by investigator.
  5. Serious bacterial infection requiring systemic antibiotics.
  6. Pregnancy
  7. Expected non-compliance.
  8. Uncontrolled illness including, but not limited to, ongoing infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.
  9. Bleeding esophageal or gastric varices within three months without ligation or sclerosis injection therapy.
  10. Subjects with known HIV infection.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: TACE alone arm
TACE (Transarterial Chemoembolization)
Procedure: TACE
Transarterial chemoembolization
Experimental: adagloxad simolenin arm
TACE plus adagloxad simolenin/OBI-821 adjuvant therapy
Procedure: TACE
Transarterial chemoembolization
Biological: adagloxad simolenin/OBI-821

Adagloxad simolenin (OBI-822) is a glyco-conjugated protein comprised of a carbohydrate tumor antigen. Globo H allyl glycoside is covalently linked to a carrier protein KLH, presented in a dominant trimer form with molecular weight between 1200-1395 kDa., to form Adagloxad simolenin (OBI-822) (Globo H-KLH) OBI-821 is a saponin based adjuvant structurally similar to descriptions found in the literature for another adjuvant, QS-21.

Adagloxad simolenin will be mixed with OBI-821 before administration.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
time-to-ITTVP
Time Frame: From enrollment till 36 months of follow-up.
time-to-intrahepatic total tumor volume progression
From enrollment till 36 months of follow-up.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chang Gung Memorial Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chau-Ting Yeh, MD, LinKou Chang Gung Menorial 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 26, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 23, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CGMH/TMUH/VGH-OBI822-HCC001

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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Conditions

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