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

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ClinicalTrials.gov Identifier: NCT03608878
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Chau-ting, Yeh, Chang Gung Memorial Hospital

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: adagloxad simolenin/OBI-821 Procedure: TACE Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 26, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020
Arms and Interventions
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Arm Intervention/treatment
Active Comparator: TACE alone arm
TACE (Transarterial Chemoembolization)
 Procedure: TACE
Transarterial chemoembolization
Experimental: adagloxad simolenin arm
TACE plus adagloxad simolenin/OBI-821 adjuvant therapy
 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.


Procedure: TACE
Transarterial chemoembolization


Outcome Measures
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Primary Outcome Measures :
  1. time-to-ITTVP [ Time Frame: From enrollment till 36 months of follow-up. ]
    time-to-intrahepatic total tumor volume progression


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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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): NCT03608878


Contacts
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Contact: Chau-Ting Yeh, MD 886 3 3281200 ext 8125 chauting@adm.cgmh.org.tw

Locations
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Taiwan
Linkou Chang Gung Memorial Hospital Recruiting
Taoyuan City, Taoyuan, Taiwan, 333
Contact: Chau-Ting Yeh, MD    886 3 3281200 ext 8121    cgaytubg@adm.cgmh.org.tw   
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
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Principal Investigator: Chau-Ting Yeh, MD LinKou Chang Gung Menorial Hospital
More Information
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Responsible Party: Chau-ting, Yeh, Director, Liver Research Center; Professor, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT03608878    
Other Study ID Numbers: CGMH/TMUH/VGH-OBI822-HCC001
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
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