Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)

NCT ID: NCT02997956

Last Updated: 2017-04-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-31
• Study Completion Date: 2022-07-31

Brief Summary

This is a phase IB study design planned to identify the MTD (Maximum Tolerated Dose) of Tocilizumab in HCC (Hepatocellular Carcinoma) patients followed by a phase II design whereupon the primary objective will be median progression free survival (PFS).

Detailed Description

TACE (Transarterial Chemo Embolization) has shown to improve overall survival compared to non-treated patients with intermediate HCC (Hepatocellular Carcinoma) tumors. However, TACE is not considered a curative strategy and eventual local recurrence is observed in nearly all (>95%) of cases. Therefore, significant clinical equipoise exists in this large group of HCC patients such that novel therapies can be tested in an adjuvant manner to TACE. Based on pre-clinical data in HCC and the increasing identification that IL-6 signaling leads to tumor progression or local recurrence in other solid malignancies, significant rationale exists for the use of Tocilizumab, an IL-6 receptor inhibitor adjuvant to TACE. While Tocilizumab has been demonstrated to be safe in RA patients and is FDA approved, limited data exists for the maximum tolerated dose (MTD) in patients with cirrhosis and HCC. Therefore, a lead in phase IB study design is planned to identify the MTD of Tocilizumab in HCC patients followed by expansion to the phase II component whereupon the primary objective will be median progression free survival (PFS).

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab

Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.

The first part of the trial will be Phase Ib and will enroll 18 participants. Participants will receive TACE on day 1 and Tocilizumab at dose level 1, 2, or 3 on days 1, 29 and 57. Maximum tolerated dose (MTD) of Tocilizumab will be determined.

The second part of the trial will be a Phase II and will enroll 50 subjects. Participants will receive TACE on day 1 and Tocilizumab at the MTD on days 1, 29 and 57.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.

Transcatheter Arterial Chemoembolization

Intervention Type: PROCEDURE

Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply

Interventions

Tocilizumab

Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.

Intervention Type: DRUG

Transcatheter Arterial Chemoembolization

Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply

Intervention Type: PROCEDURE

Other Intervention Names

ACTEMRA; TACE

Eligibility Criteria

Inclusion Criteria

• Histologic evidence of HCC, Barcelona-Clinic Liver Cancer (BCLC) stage B
• FFPE (Fixed-paraffin Embedded) tumor tissue (two cores preferred) for biomarker analysis
• Prior radioembolization, local ablative therapies (radiofrequency, microwave or cryoablation), radiation (external beam or stereotactic), or hepatic resection permitted if completed ≥ 4 weeks prior to study enrollment and if patient has recovered with ≤ grade 1 toxicity and if untreated measurable disease is present.
• Radiographically measurable disease by mRECIST in at least one site not previously treated by local therapies.
• Must not be receiving treatment with other investigational agents and must not have received any other investigational agent's ≤ 4 weeks prior to registration.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Required lab and acceptable range criteria.
• Women of child-bearing potential and men must agree to use 2 methods of adequate contraception.
• No contraindications to TACE therapy
• Child-Pugh Score A-B
• Ability to understand and the willingness to sign a written informed consent, and the willingness to comply with the requirements of the protocol.
• Life expectancy greater than 3 months.
• Adequate baseline organ and marrow function

Exclusion Criteria

• History of hepatitis B
• Women must not be pregnant or breastfeeding
• Presence of other malignancies
• Active or history of Tuberculosis
• Patients with known HIV positive status
• Conditions with impaired immunity or on immunosuppressive medications such as oral steroids, calcineurin inhibitors, or anti-proliferative agents.
• Must have no evidence of significant, uncontrolled concomitant diseases
• Must have no ongoing or active, uncontrolled infections

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Theodore Welling, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

The University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

HUM00104809

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2015.105

Identifier Type: -

Identifier Source: org_study_id