Clinical trial NCT02997956: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2016-12-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Maximum Tolerated Dose of Tocilizumab
timeFrame: 84 Days Post Treatment
measure: Median Progression Free Survival
timeFrame: 2 Years Post Treatment
Secondary outcomes:
measure: Number of patients that respond to treatment
timeFrame: 2 Years Post Treatment
measure: Number of patients alive at two years post treatment
timeFrame: 2 Years Post Treatment
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Theodore Welling, M.D.
role: PRINCIPAL_INVESTIGATOR
References: