Hepatocellular CarcinomaPhase 2NCT03608878
Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in HCC Patients With GALNT14-rs9679162-non-TT Genotype
A Phase 2 study testing adagloxad simolenin/OBI-821 and TACE in people with Hepatocellular Carcinoma, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- adagloxad simolenin/OBI-821 and TACE
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteTaiwan
- Study dates
- 26 Apr 2019to 31 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed Diagnosis of HCC
- Has a Globo-H or SSEA-3 positive tumor as determined by IHC
- Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.
- 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.
- Child-Pugh functional class A or B.
- GALNT14- rs9679162 "non TT" genotype
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- At least 1 measurable lesion must be present.
- ECOG performance status 0 to 1.
- Age > 20 years
- 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
- Informed consent must be obtained prior to perform any study procedure.
- Total bilirubin < 3.0 mg/dL with no evidence of biliary tract obstruction.
- Appropriate Serum alanine aminotransferase, aspartate aminotransferase, Absolute neutrophil count, Platelets and Serum creatinine
- Antiviral treatment for hepatitis B or C is allowed except for interferon.
Who cannot join
- BCLC stage A.
- Presence of extrahepatic metastasis or main portal vein thrombosis.
- Child-Pugh score = C.
- Significant cardiac disease as determined by investigator.
- Serious bacterial infection requiring systemic antibiotics.
- Pregnancy
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- Expected non-compliance.
- Uncontrolled illness including, but not limited to, ongoing infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness.
- Bleeding esophageal or gastric varices within three months without ligation or sclerosis injection therapy.
- Subjects with known HIV infection.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- adagloxad simolenin/OBI-821, TACE
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adagloxad simolenin/OBI-821Biological
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.
TACEProcedure or surgery
Transarterial chemoembolization
| Study group | Role | What they receive |
|---|---|---|
| TACE alone arm | Active comparator | TACE (Transarterial Chemoembolization) Receives: Procedure: TACE |
| adagloxad simolenin arm | Experimental | TACE plus adagloxad simolenin/OBI-821 adjuvant therapy Receives: Biological: adagloxad simolenin/OBI-821; Procedure: TACE |
What is being measured
The primary outcome is the main question the study is designed to answer.
time-to-ITTVP
time-to-intrahepatic total tumor volume progression
Measured: From enrollment till 36 months of follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2018
- Study start26 Apr 2019
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Why it stopped: The biopsies in the first 5 screened patients were all negative for Globo-H, of which positive is required to include the patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chau-ting, Yeh, Chang Gung Memorial Hospital
- Investigators
- Chau-Ting Yeh, MD, Principal investigator, LinKou Chang Gung Menorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03608878
- Sponsor's protocol ID
- CGMH/TMUH/VGH-OBI822-HCC001
- Status last verified
- May 2021
- First submitted
- 23 Jul 2018
- Last updated
- 6 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03608878
- Acronym / sponsor ID
- CGMH/TMUH/VGH-OBI822-HCC001
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The biopsies in the first 5 screened patients were all negative for Globo-H, of which positive is required to include the patients.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 26 Apr 2019 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 1 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TACE alone arm | Active comparator | Procedure: TACETACE (Transarterial Chemoembolization) |
| adagloxad simolenin arm | Experimental | Biological: adagloxad simolenin/OBI-821, Procedure: TACETACE plus adagloxad simolenin/OBI-821 adjuvant therapy |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Confirmed Diagnosis of HCC
- Has a Globo-H or SSEA-3 positive tumor as determined by IHC
- Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.
- 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.
- Child-Pugh functional class A or B.
Key exclusion criteria (10 listed)
- BCLC stage A.
- Presence of extrahepatic metastasis or main portal vein thrombosis.
- Child-Pugh score = C.
- Significant cardiac disease as determined by investigator.
- Serious bacterial infection requiring systemic antibiotics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adagloxad simolenin/OBI-821Adagloxad 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. | Biological | adagloxad simolenin arm |
| TACETransarterial chemoembolization | Procedure or surgery | TACE alone arm, adagloxad simolenin arm |
Primary outcome
time-to-ITTVP
Time frame: From enrollment till 36 months of follow-up.
time-to-intrahepatic total tumor volume progression
Results and safety
The study was stopped early (reason given: The biopsies in the first 5 screened patients were all negative for Globo-H, of which positive is required to include the patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chau-Ting Yeh, MD principal investigator
LinKou Chang Gung Menorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing adagloxad simolenin/OBI-821 and TACE in people with Hepatocellular Carcinoma, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The biopsies in the first 5 screened patients were all negative for Globo-H, of which positive is required to include the patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time-to-ITTVP (time frame: From enrollment till 36 months of follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.