AzTrials
AzTrials

Heptocellular CancerPhase 1/2NCT01853618

Tremelimumab With Chemoembolization or Ablation for Liver Cancer

A Phase 1/2 study testing Tremelimumab, RFA and TACE in people with Heptocellular Cancer and Biliary Tract Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Background: Tremelimumab is a cancer treatment drug that helps the immune system recognize and destroy cancer cells. Researchers want to see if it can be used to treat advanced liver cancer. The drug will be given with one of two types of treatment for liver cancer. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Tremelimumab, RFA and TACE
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
2 May 2013to 7 Jun 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Patients who have had standard of care chemotherapy, large field radiotherapy, or major surgery must wait 2 weeks prior to entering the study. For recent experimental therapies a 28 day period of time must elapse before treatment.
  • Patients who have undergone prior liver transplantation are ineligible.
  • Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of chronic autoimmune disease (e.g., Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, rheumatoid arthritis, hypophysitis, etc.) with symptomatic disease within the 3 years before randomization. Note: Active vitiligo or a history of vitiligo will not be a basis for exclusion.
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.
Show all 16Show fewer
  • Diverticulitis (either active or history of) within the past 2 years. Note that diverticulosis is permitted.
  • Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis.
  • Currently receiving immunosuppressive doses of steroids or other immunosuppressive medications (inhaled and topical steroids are permitted)
  • History of sarcoidosis syndrome
  • Patients should not be vaccinated with live attenuated vaccines within 1 month of starting Tremelimumab treatment.
  • 12 Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • 13. HIV-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and Tremelimumab. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that Tremelimumab may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events.
  • 14. History of hypersensitivity reaction to human or mouse antibody products.
  • 15. Pregnancy and breast feeding are exclusion factors. The effects of Tremelimumab on the developing human fetus are unknown. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • 16. Patients with unhealed surgical wounds for more than 30 days.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Study of Tremelimumab - A Monoclonal Antibody Against CTLA-4 in Combination With Trans-Arterial Catheter Chemoembolization (TACE), Radiofrequency Ablation (RFA), or Cryoablation in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)

Background:

  • Tremelimumab is a cancer treatment drug that helps the immune system recognize and destroy cancer cells. Researchers want to see if it can be used to treat advanced liver cancer. The drug will be given with one of two types of treatment for liver cancer. The first type, transarterial catheter chemoembolization (TACE), injects chemotherapy drugs into the tumor through the main blood vessel that is feeding it. That blood vessel is then closed off to help keep the drugs in the tumor longer. The second type, radiofrequency ablation (RFA), uses a heated probe to destroy the tumor tissue. Researchers want to study how safe and effective these treatments are with the study drug.
Read more

Objectives:

  • To test the safety and effectiveness of Tremelimumab with TACE or RFA for advanced liver cancer.

Eligibility:

  • Individuals at least 18 years of age who have advanced liver cancer that has not responded to other treatments.
Read the detailed description

Background:

Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. For patients with advanced disease sorafenib is the only approved drug and this has limited benefit.

Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.

Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. Both transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA) have been shown to do this, as well as cryoablation and external beam radiation.

The underlying hypothesis of this study is that the effect of anti-CTLA4 treatment can be enhanced by TACE or RFA in patients with advanced hepatocellular carcinoma. We will also evaluate this in the context of cryoablation and radiation in hepatocellular carcinoma (HCC) and RFA in cholangiocarcinoma.

Objective:

To assess the safety and feasibility of combining Tremelimumab with trans-arterial catheter chemoembolization (TACE) radiofrequency ablation (RFA), or cryoablation in patients with advanced HCC.

Eligibility:

Histologically or cytologically confirmed diagnosis of HCC.

Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.

Barcelona Clinic Liver Cancer (BCLC) Stage B and C patients.

Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

Being tested
Tremelimumab, RFA, TACE, Cryoablation
Keywords
Blocking of Immune Suppression, Monoclonal Antibody, Immunotherapy, Ablative Therapy
Medical subject headings
Biliary Tract Neoplasms, Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TremelimumabDrug

    Also called Ticilimumab

    3.5 mg/kg or 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

  • RFAProcedure or surgery

    Also called Radiofrequency Ablation

    Performed on Day 36

  • TACEProcedure or surgery

    Also called Transarterial Catheter Chemoembolization

    Performed on Day 36 and may be repeated (as per standard of care) on months 3, 7, and 13, and every (q)6 months thereafter (if indicated)

  • CryoablationProcedure or surgery

    Performed on Day 36

Study groups in NCT01853618
Study groupRoleWhat they receive
Pilot 1/Arm A1-Tremelimumab + RFA or TACEExperimentalEscalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
Receives: Drug: Tremelimumab; Procedure: RFA; Procedure: TACE
2/Arm A2 - Tremelimumab + RFA or TACEExperimentalTremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
Receives: Drug: Tremelimumab; Procedure: RFA; Procedure: TACE
3/Arm B - Tremelimumab + TACEExperimentalTremelimumab + Transarterial Catheter Chemoembolization (TACE)
Receives: Drug: Tremelimumab; Procedure: TACE
4/Arm C (never opened)ExperimentalTremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
Receives: Drug: Tremelimumab; Procedure: TACE; Procedure: Cryoablation
5/Arm D - Tremelimumab + CryoablationExperimentalTremelimumab + Cryoablation
Receives: Drug: Tremelimumab; Procedure: Cryoablation
6/Arm E - Tremelimumab + RFAExperimentalTremelimumab + Radiofrequency Ablation (RFA)
Receives: Drug: Tremelimumab; Procedure: RFA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Serious and Non-Serious Adverse Events Regardless of Attribution

    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Measured: Date treatment consent signed to date off study, approximately 44 months and 5 days for 1/Arm A1; 49 months and 26 days for 2/Arm A2; 1 month and 26 days for 3/Arm B; 30 months and 20 days for 5/Arm D; and 34 months and 25 days for 6/Arm E.

Secondary outcomes (3)

  1. Number of Participants With Best Response

    Best response was assessed by the combined Response Evaluation Criteria in Solid Tumors (RECIST and the Modified Immune-Related Response Criteria (irRC). Complete Response (CR) is disappearance of all target lesions. Any patjhological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if it is the smallest on study). The appearance of one or more lesions is also considered progressions.

    Measured: Start of study, baseline target lesions until disease progression occurs with 20% increase of target lesions or appearance of new lesions, up to 13.1 months

  2. Progression Free Survival (PFS)

    Progression free survival is defined as the amount of time a subject survives without disease progression after treatment. Progression is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if it is the smallest on study). The appearance of one or more lesions is also considered progressions.

    Measured: Progression free survival is time patients were off treatment until death. For all cohorts progression free survival ranged from 3.4 months to 8.6 months

  3. Overall Survival

    Overall survival is defined as the amount of time a subject survives after therapy.

    Measured: From the time of initial treatment consent until date of death for each patient. Overall survival ranged from 6 months to 13.1 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2013 (estimated)
  2. Study start2 May 2013
  3. Primary completion7 Jun 2017
  4. Study completion7 Jun 2017

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01853618
Sponsor's protocol ID
130120
Other IDs
13-C-0120
Status last verified
Nov 2019
First submitted
2 May 2013
Last updated
10 Dec 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001 Oct 15;94(2):153-6. doi: 10.1002/ijc.1440. No abstract available.

    PubMed 11668491

  • Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.

    PubMed 18477802

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Xie C, Duffy AG, Mabry-Hrones D, Wood B, Levy E, Krishnasamy V, Khan J, Wei JS, Agdashian D, Tyagi M, Gangalapudi V, Fioravanti S, Walker M, Anderson V, Venzon D, Figg WD, Sandhu M, Kleiner DE, Morelli MP, Floudas CS, Brar G, Steinberg SM, Korangy F, Greten TF. Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer. Hepatology. 2019 May;69(5):2048-2060. doi: 10.1002/hep.30482. Epub 2019 Mar 10.

    PubMed 30578687

  • Agdashian D, ElGindi M, Xie C, Sandhu M, Pratt D, Kleiner DE, Figg WD, Rytlewski JA, Sanders C, Yusko EC, Wood B, Venzon D, Brar G, Duffy AG, Greten TF, Korangy F. The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma. Cancer Immunol Immunother. 2019 Apr;68(4):599-608. doi: 10.1007/s00262-019-02299-8. Epub 2019 Jan 28.

    PubMed 30688989

  • Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, Davis JL, Hughes MS, Heller T, ElGindi M, Uppala A, Korangy F, Kleiner DE, Figg WD, Venzon D, Steinberg SM, Venkatesan AM, Krishnasamy V, Abi-Jaoudeh N, Levy E, Wood BJ, Greten TF. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017 Mar;66(3):545-551. doi: 10.1016/j.jhep.2016.10.029. Epub 2016 Nov 2.

    PubMed 27816492

  • Greten TF, Sangro B. Targets for immunotherapy of liver cancer. J Hepatol. 2017 Sep 18:S0168-8278(17)32287-0. doi: 10.1016/j.jhep.2017.09.007. Online ahead of print.

    PubMed 28923358

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tremelimumab, RFA and TACE in people with Heptocellular Cancer and Biliary Tract Neoplasms, run by National Cancer Institute (NCI) 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 0 inclusion and 16 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: finished, as of the sponsor's last update on 10 Dec 2019. 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?

Yes. Results are posted in the registry (first posted 10 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Serious and Non-Serious Adverse Events Regardless of Attribution (time frame: Date treatment consent signed to date off study, approximately 44 months and 5 days for 1/Arm A1; 49 months and 26 days for 2/Arm A2; 1 month and 26 days for 3/Arm B; 30 months and 20 days for 5/Arm D; and 34 months and 25 days for 6/Arm E.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01853618, which also lists 7 linked publications.

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 10 Dec 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in