Hepatocellular CarcinomaPhase 1/2NCT02997956
Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)
A Phase 1/2 study testing Tocilizumab and Transcatheter Arterial Chemoembolization in people with Hepatocellular Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Tocilizumab and Transcatheter Arterial Chemoembolization
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2017to Jul 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: Phase IB/II Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)
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).
Read the 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
- Being tested
- Tocilizumab, Transcatheter Arterial Chemoembolization
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called ACTEMRA
Participants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57.
Transcatheter Arterial ChemoembolizationProcedure or surgery
Also called TACE
Minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | 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. Receives: Drug: Tocilizumab; Procedure: Transcatheter Arterial Chemoembolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 84 Days Post Treatment
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.
Measured: 2 Years Post Treatment
Secondary outcomes (2)
Number of patients that respond to treatment
Number of patients that respond to treatment
Measured: 2 Years Post Treatment
Number of patients alive at two years post treatment
Number of patients alive at two years post treatment
Measured: 2 Years Post Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study startJul 2017 (estimated)
- Primary completionJul 2020 (estimated)
- Study completionJul 2022 (estimated)
Why it stopped: funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Theodore Welling, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02997956
- Sponsor's protocol ID
- UMCC 2015.105
- Other IDs
- HUM00104809
- Status last verified
- Apr 2017
- First submitted
- 16 Dec 2016
- Last updated
- 25 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IB/II Study of Tocilizumab in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)
- ClinicalTrials.gov ID
- NCT02997956
- Acronym / sponsor ID
- UMCC 2015.105
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: funding issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Jul 2017 (estimated)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: Tocilizumab, Procedure: Transcatheter Arterial ChemoembolizationParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: ACTEMRAParticipants will receive Tocilizumab (ACTEMRA®) at 4, 6, or 8 mg/kg IV dose escalation on days 1, 29 and 57. | Drug | Tocilizumab |
| Transcatheter Arterial ChemoembolizationAlso: TACEMinimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply | Procedure or surgery | Tocilizumab |
Primary outcome
Maximum Tolerated Dose of Tocilizumab
Time frame: 84 Days Post Treatment
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
Time frame: 2 Years Post Treatment
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 secondary outcomes
Number of patients that respond to treatment
Time frame: 2 Years Post Treatment
Number of patients alive at two years post treatment
Time frame: 2 Years Post Treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theodore Welling, M.D. principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tocilizumab and Transcatheter Arterial Chemoembolization in people with Hepatocellular Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of Tocilizumab (time frame: 84 Days Post Treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2017.