A Randomized Double-blind, Placebo-controlled Japanese Phase III Trial of ARQ 197 in Hepatocellular Carcinoma (HCC) (JET-HCC)

• ClinicalTrials.gov Identifier: NCT02029157
• Recruitment Status: Completed
• First Posted: January 7, 2014
• Last Update Posted: October 9, 2017
• Sponsor: Kyowa Kirin Co., Ltd.
• Information provided by (Responsible Party): Kyowa Kirin Co., Ltd.

Tracking Information

• First Submitted Date: December 27, 2013
• First Posted Date: January 7, 2014
• Last Update Posted Date: October 9, 2017
• Study Start Date: January 2014
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 6, 2014)

Progression-free survival (PFS) [ Time Frame: Estimated median of 8-12 weeks in PFS ]

Progression-free survival will be compared between ARQ 197 group and Placebo group, to prove the efficacy of ARQ 197 in the population.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 6, 2014)

Overall survival [ Time Frame: Estimated median of 24 weeks in overall survival ]

The date of the events was followed every three months after the end of the treatments of the study drug.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Randomized Double-blind, Placebo-controlled Japanese Phase III Trial of ARQ 197 in Hepatocellular Carcinoma (HCC)
• Official Title: A Phase III Randomized Double-blind, Placebo-controlled Trial of ARQ 197 in Subjects With c-MET Diagnostic-high Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Sorafenib Therapy
• Brief Summary: The present clinical trial is aiming to evaluate efficacy of ARQ 197 in patients with hepatocellular carcinoma (HCC), who were resistant or intolerable to one systemic chemotherapy regimen including sorafenib.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Liver Cancer

Intervention

• Drug: ARQ197
• Drug: Placebo

Study Arms

• Experimental: ARQ 197
  Daily oral dose
  Intervention: Drug: ARQ197
• Placebo Comparator: Placebo
  Daily oral dose
  Intervention: Drug: Placebo

• Publications *: Kudo M, Morimoto M, Moriguchi M, Izumi N, Takayama T, Yoshiji H, Hino K, Oikawa T, Chiba T, Motomura K, Kato J, Yasuchika K, Ido A, Sato T, Nakashima D, Ueshima K, Ikeda M, Okusaka T, Tamura K, Furuse J. A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma. Cancer Sci. 2020 Oct;111(10):3759-3769. doi: 10.1111/cas.14582. Epub 2020 Aug 26.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2017): 386
• Original Estimated Enrollment (submitted: January 6, 2014): 160
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Informed consent form
• ≥20 years old
• Inoperable HCC which is not eligible for locoregional therapy
• Diagnosed as c-Met high in tumor sample
• Radiographic progression is confirmed during or after systemic chemotherapy including sorafenib, or those who are intolerance to the chemotherapy.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or 1
• Child-Pugh Class A
• Having measurable target lesions which are defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
• Negative pregnancy test results
• Adequate organ function
• Life expectancy of at least 12 weeks

Exclusion Criteria:

• More than 2 prior systemic chemotherapy.
• Prior therapy of c-Met inhibitor (including antibody)
• Any systemic therapy within ≤2 weeks prior to the randomization
• Locoregional therapy within ≤4 weeks prior to randomization.
• Major surgery within ≤4 weeks prior to the randomization
• Concurrent cancer within ≤5 years prior to the randomization
• History of cardiac diseases
• Active clinically serious infections defined as ≥ Grade 3 according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0
• Any psychological disorder affecting Informed Consent
• Diagnosis positive for anti-HIV antibody and/or anti-HTLV-1 antibody
• Blood or albumin transfusion within ≤14 days prior to the screening test
• Concurrent interferon therapy against Hepatitis B Virus (HBV)/ Hepatitis C Virus (HCV)
• Symptomatic brain metastases
• History of liver transplantation
• Inability to swallow oral medications
• Confirmed interstitial lung disease
• Pleural effusion and/or clinically significant ascites
• Pregnancy or breast-feeding
• Without consent to effective single or combined contraceptive methods

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02029157
• Other Study ID Numbers: ARQ 197-009
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kyowa Kirin Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Kyowa Kirin Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kyowa Kirin Co., Ltd.
• Verification Date: October 2017