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

Hepatocellular Carcinoma Clinical Trial

Official title:

Phase IB/II Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02997956
• Other study ID #: UMCC 2015.105
• Secondary ID: HUM00104809
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: December 16, 2016
• Last updated: April 21, 2017
• Start date: July 2017
• Est. completion date: July 2022

Study information

• Verified date: April 2017
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2022
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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

Procedure:
• Transcatheter Arterial Chemoembolization
Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply

Locations

Country	Name	City	State
United States	The University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	84 Days Post Treatment
Primary	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.	2 Years Post Treatment
Secondary	Number of patients that respond to treatment	Number of patients that respond to treatment	2 Years Post Treatment
Secondary	Number of patients alive at two years post treatment	Number of patients alive at two years post treatment	2 Years Post Treatment