Study of Y90-Radioembolization With Nivolumab in Asians With Hepatocellular Carcinoma

NCT03033446 | Active Not Recruiting Phase 2

• 1 other identifier: CA209-678
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of liver-localised radioembolization and nivolumab on liver cancer.

Conditions

HepatoCellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Tumour assessment at 8 weeks

Secondary Outcomes (8)

• Time to Response

  From date of first dose with Y90 Radioemolization (RE) until best overall response of Complete Response (CR) or Partial Response (PR) is achieved, up to 12 weeks after last dose of Nivolumab

• Duration of Response

  From date of first assessment of CR or PR until the first date that progressive disease or death is documented, up to 2 years

• Time to Progression

  From date of first dose with Y90 RE until the first date that progressive disease is documented, up to 12 weeks after last dose of Nivolumab

• Progression Free Survival

  From date of first dose with Y90 RE until tumour progression, or death from any cause, up to 12 weeks after last dose of Nivolumab

• Overall Survival

  From date of first dose with Y90 RE until death from any cause, up to 2 years

Study Arms (1)

Y90-Radioembolization and Nivolumab

EXPERIMENTAL

Radiation: Y-90 Radioembolization; Drug: Nivolumab

Interventions

Y-90 Radioembolization RADIATION

Dose of Yttrium-90 is determined based on BSA, size of liver tumor, and dose modifications required for percent lung shunting between 10-20% on the Tc-99MMA scan

Also known as: Selective Internal Radiation Therapy

Y90-Radioembolization and Nivolumab

Nivolumab DRUG

21 days after Radioembolization, 240mg of IV Nivolumab over 30 minutes will be administered every 2 weeks

Also known as: Opdivo

Y90-Radioembolization and Nivolumab

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hepatocellular carcinoma (HCC) that is not suitable for resection or liver transplant, who are planned for Y90 radioembolization as per institutional practice.
• Patients must have measurable disease with target lesion in liver, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Diagnosis of HCC confirmed by histology/cytology or clinically by AASLD criteria in cirrhotic subjects. Patients without cirrhosis require histological confirmation of diagnosis
• No prior Y90 radioembolization therapy. Prior local therapies, such as surgery, hepatic artery embolization/chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoabalastion is allowed, if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan
• Age ≥ 21 years.
• ECOG performance status ≤ 2
• Life expectancy of greater than 3 months
• Only patients with Child-Pugh score for liver cirrhosis of A (sum of scores for five parameters: 5-6) will be allowed into this trial
• Subjects with HBV infection must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. Both HBeAg positive and negative subjects will be included.
• Patients must have lesions in the liver that are amenable to CT-guided liver biopsy
• Patients must have normal organ and marrow function as defined below:
• Haemoglobin ≥ 8.5g/dL
• Absolute Neutrophil Count ≥ 1.5 x 10\^9/L
• Platelets ≥ 50 x 10\^9/L
• Total Bilirubin \< 3 mg/dL

You may not qualify if:

• Patients are excluded if they are receiving any other investigational agents or using an investigational device within 4 weeks of first dose of treatment. Patients are excluded if they are receiving other systemic therapy within 2 weeks of first dose of treatment.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Prior use of anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any drug specifically targeted T-cell costimulatory checkpoint pathways
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with any active autoimmune disease or history of known or suspected autoimmune disease requiring systemic therapy within the past 2 years, except for subjects with vitiligo, resolved childhood asthma/atopy or euthyroid patients with a history of Grave's disease (subjects with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to randomization). Replacement therapy (e.g. with thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc) is not considered a form of systemic treatment
• Pregnant women or breastfeeding mothers are excluded from this study because of the potential risks to the foetus or baby. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Diagnosis of immunodeficiency, including HIV/AIDS
• Prior organ allograft or allogeneic bone marrow transplantation
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
• Inability to comply with restrictions and prohibited activities/treatments in this study
• Chronic treatment with systemic steroids or other immunosuppressive agent.
• Subjects with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, in situ cervical cancers, localized prostate cancer or in situ breast cancer) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required
• Prior radiation therapy to the liver or upper abdomen

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre - Singapore

Singapore, 169610, Singapore

Location

Related Publications (1)

• Tai D, Loke K, Gogna A, Kaya NA, Tan SH, Hennedige T, Ng D, Irani F, Lee J, Lim JQ, Too CW, Ng MCH, Tham CK, Lam J, Koo SL, Chong HS, Goh GB, Huang HL, Venkatanarasimha N, Lo R, Chow PKH, Goh BKP, Chung A, Toh HC, Thng CH, Lim TKH, Yeong J, Zhai W, Chan CY, Choo SP. Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): a single arm, single centre, phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1025-1035. doi: 10.1016/S2468-1253(21)00305-8. Epub 2021 Oct 23.

  PMID: 34695377 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Wai-Meng TAI, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 26, 2017
• Study Start: December 20, 2016
• Primary Completion: August 31, 2019
• Study Completion: December 31, 2025
• Last Updated: January 6, 2025

Record last verified: 2025-01

Locations

SG (1)