A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Hepatocellular Carcinoma

NCT03586973 | Completed Phase 2 Results

• 3 other identifiers: Cabozantinib-2003U1111-1214-6141JapicCTI-184018
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 17

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of cabozantinib in Japanese participants with advanced hepatocellular carcinoma (HCC) who have received prior systemic anticancer therapy.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 24-Week Progression-Free Survival Rate (PFSR)

  24-week PFSR=percentage of participants with progression-free survival (PFS) of at least 24 weeks at Week 25 Day 1 plus 7 days. PFS=time from first day of study drug administration to earlier of progressive disease (PD) or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1(RECIST 1.1). PD=at least a 20% increase in sum of target lesion diameters (SoD) with reference to smallest(nadir) SoD. In addition to relative increase of 20%, SoD must also demonstrate an absolute increase of at least 5 mm. For nontarget lesion time Point Response, unequivocal progression of nontarget lesions. Modest 'increase' in size of one or more nontarget lesions is usually not sufficient to quality for unequivocal progression status, it must not be representative of single lesion increase. Lesion in an anatomical location and not scanned at baseline is considered new lesion. Lesion qualifies as PD if finding is unequivocally not due to change in imaging technique or modality.

  Week 25 Day 1 plus 7 days

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Until disease progression, or death or end of study (Up to approximately 2.8 years)

• Objective Response Rate (ORR)

  Up to approximately 2 years

• Disease Control Rate (DCR)

  Up to approximately 2 years

• Overall Survival (OS)

  Up to end of study (Up to approximately 2.8 years)

Study Arms (2)

Cohort A: Cabozantinib 60 mg

EXPERIMENTAL

Participants who have received first/second line anticancer therapy with sorafenib were assigned to Cohort A and received cabozantinib 60 milligrams (mg), tablet, orally, once daily in the fasted state, up to approximately 2 years.

Drug: Cabozantinib

Cohort B: Cabozantinib 60 mg

EXPERIMENTAL

Participants who did not receive first/second line anticancer therapy with sorafenib were assigned to Cohort B and received cabozantinib 60 mg, tablet orally, once daily in the fasted state, up to approximately 2 years.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib tablet

Also known as: XL184

Cohort A: Cabozantinib 60 mg; Cohort B: Cabozantinib 60 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Japanese participants 20 years of age or older on the day of consent.
• Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted).
• Measurable disease per response evaluation criteria in solid tumors (RECIST) 1.1 as determined by the investigator.
• Participants who have disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation).
• Participants who have received 1 or 2 prior anticancer therapies for advanced HCC.
• Cohort A: participants who have received prior sorafenib.
• Cohort B: participants who have not received prior sorafenib. Note: Additional prior systemic therapies used as adjuvant or local therapy are allowed.
• Radiographic progression following prior systemic anticancer therapy for advanced HCC.
• Recovery to =\<Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 from toxicities related to any prior treatments, unless the Adverse Events (AEs) are clinically nonsignificant and/or stable on supportive therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and life expectancy of at least 3 months.
• Child-Pugh Score of A.
• Adequate organ and marrow function at Screening (within 10 days before Week 1 Day 1):
• Absolute neutrophil count (ANC) \>=1,200/mm\^3.
• Platelets \>=60,000/mm\^3.
• Hemoglobin \>=8 g/dL.

You may not qualify if:

• Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
• Any type of anticancer agent within 14 days before the first day of study drug administration (Week 1 Day 1).
• Radiation therapy within 28 days (14 days for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 42 days before Week 1 Day 1 (participant is excluded if there are any clinically relevant ongoing complications from prior radiation therapy).
• Prior Cabozantinib treatment.
• Treatment with any investigational products (excluding anticancer products approved in Japan) within 28 days before Week 1 Day 1.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before Week 1 Day 1. Eligible participants must be without corticosteroid treatment at Week 1 Day 1.
• Concomitant anticoagulation, with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel).
• Note: Low-dose aspirin for prophylactic use (per local applicable guidelines) and low-dose, low molecular weight heparins (LMWH) are permitted (LMWH has not been approved for the use for cardioprotection in Japan). Anticoagulation with therapeutic doses of LMWH is allowed in participants without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before Week 1 Day 1, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
• Participants who have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including
• Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \>150 mm Hg systolic, or \>100 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other ischemic event within 6 months before Week 1 Day 1.
• Thromboembolic event within 3 months before Week 1 Day 1.
• A left-ventricular ejection fraction =\<50%.

Sponsors & Collaborators

• Takeda: lead

Study Sites (17)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

Iizuka Hospital

Iizuka, Fukuoka, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, Japan

Location

Sapporo-Kosei General Hospital

Sapporo, Hokkaido, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Location

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan

Location

Kindai University Hospital

Sayama, Osaka, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Location

Kyorin University Hospital

Mitaka, Tokyo, Japan

Location

Japanese Red Cross Musashino Hospital

Musashino, Tokyo, Japan

Location

Chiba University Hospital

Chiba, Japan

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Okayama University Hospital

Okayama, Japan

Location

Osaka City University Hospital

Osaka, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Related Publications (1)

• Kudo M, Tsuchiya K, Kato N, Hagihara A, Numata K, Aikata H, Inaba Y, Kondo S, Motomura K, Furuse J, Ikeda M, Morimoto M, Achira M, Kuroda S, Kimura A. Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: a phase 2 multicenter study. J Gastroenterol. 2021 Feb;56(2):181-190. doi: 10.1007/s00535-020-01753-0. Epub 2021 Jan 3.

  PMID: 33392749 DERIVED

MeSH Terms

Interventions

cabozantinib

Results Point of Contact

• Title: Study Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 16, 2018
• Study Start: August 6, 2018
• Primary Completion: July 17, 2019
• Study Completion: June 29, 2021
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (17)