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

Primary Purpose

Hepatocellular Carcinoma

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tocilizumab
Transcatheter Arterial Chemoembolization
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Michigan Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tocilizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of Tocilizumab
The MTD is defined as the dose of Tocilizumab that induces dose-limiting toxicity in 20% of subjects or less when added to TACE. Patients must complete 84 days of treatment before the dose can be escalated.
Median Progression Free Survival
Patients will be followed every 3 months for 2 years post treatment. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. Progressive disease is defined as at least a 20% increase in the sum of the LD or the appearance of one or more new lesions.

Secondary Outcome Measures

Number of patients that respond to treatment
Number of patients that respond to treatment
Number of patients alive at two years post treatment
Number of patients alive at two years post treatment

Full Information

First Posted
December 16, 2016
Last Updated
April 21, 2017
Sponsor
University of Michigan Rogel Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT02997956
Brief Title
Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)
Official Title
Phase IB/II Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Withdrawn
Why Stopped
funding issues
Study Start Date
July 2017 (Anticipated)
Primary Completion Date
July 2020 (Anticipated)
Study Completion Date
July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tocilizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
ACTEMRA
Intervention Description
Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.
Intervention Type
Procedure
Intervention Name(s)
Transcatheter Arterial Chemoembolization
Other Intervention Name(s)
TACE
Intervention Description
Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of Tocilizumab
Description
The MTD is defined as the dose of Tocilizumab that induces dose-limiting toxicity in 20% of subjects or less when added to TACE. Patients must complete 84 days of treatment before the dose can be escalated.
Time Frame
84 Days Post Treatment
Title
Median Progression Free Survival
Description
Patients will be followed every 3 months for 2 years post treatment. Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death. Progressive disease is defined as at least a 20% increase in the sum of the LD or the appearance of one or more new lesions.
Time Frame
2 Years Post Treatment
Secondary Outcome Measure Information:
Title
Number of patients that respond to treatment
Description
Number of patients that respond to treatment
Time Frame
2 Years Post Treatment
Title
Number of patients alive at two years post treatment
Description
Number of patients alive at two years post treatment
Time Frame
2 Years Post Treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theodore Welling, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

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

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