Tremelimumab With Chemoembolization or Ablation for Liver Cancer

NCT01853618 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 13012013-C-0120
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

Heptocellular Cancer; Biliary Tract Neoplasms; Liver Cancer; Hepatocellular Carcinoma; Biliary Cancer

Keywords

Blocking of Immune Suppression; Monoclonal Antibody; Immunotherapy; Ablative Therapy

Outcome Measures

Primary Outcomes (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.

  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)

• Number of Participants With Best Response

  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

• Progression Free Survival (PFS)

  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

• Overall Survival

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

Study Arms (6)

Pilot 1/Arm A1-Tremelimumab + RFA or TACE

EXPERIMENTAL

Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Drug: Tremelimumab; Procedure: RFA; Procedure: TACE

2/Arm A2 - Tremelimumab + RFA or TACE

EXPERIMENTAL

Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Drug: Tremelimumab; Procedure: RFA; Procedure: TACE

3/Arm B - Tremelimumab + TACE

EXPERIMENTAL

Tremelimumab + Transarterial Catheter Chemoembolization (TACE)

Drug: Tremelimumab; Procedure: TACE

4/Arm C (never opened)

EXPERIMENTAL

Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Drug: Tremelimumab; Procedure: TACE; Procedure: Cryoablation

5/Arm D - Tremelimumab + Cryoablation

EXPERIMENTAL

Tremelimumab + Cryoablation

Drug: Tremelimumab; Procedure: Cryoablation

6/Arm E - Tremelimumab + RFA

EXPERIMENTAL

Tremelimumab + Radiofrequency Ablation (RFA)

Drug: Tremelimumab; Procedure: RFA

Interventions

Tremelimumab DRUG

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

Also known as: Ticilimumab

2/Arm A2 - Tremelimumab + RFA or TACE; 3/Arm B - Tremelimumab + TACE; 4/Arm C (never opened); 5/Arm D - Tremelimumab + Cryoablation; 6/Arm E - Tremelimumab + RFA; Pilot 1/Arm A1-Tremelimumab + RFA or TACE

RFA PROCEDURE

Performed on Day 36

Also known as: Radiofrequency Ablation

2/Arm A2 - Tremelimumab + RFA or TACE; 6/Arm E - Tremelimumab + RFA; Pilot 1/Arm A1-Tremelimumab + RFA or TACE

TACE PROCEDURE

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)

Also known as: Transarterial Catheter Chemoembolization

2/Arm A2 - Tremelimumab + RFA or TACE; 3/Arm B - Tremelimumab + TACE; 4/Arm C (never opened); Pilot 1/Arm A1-Tremelimumab + RFA or TACE

Cryoablation PROCEDURE

Performed on Day 36

4/Arm C (never opened); 5/Arm D - Tremelimumab + Cryoablation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) or (Cohort E only) biliary tract carcinoma (BTC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma in Cohort E). Fibrolammelar variant is also allowed. For cohort E, the term BTC includes intraor extrahepatic cholangiocarcinoma, gallbladder cancer or ampullary cancer, as long as there is an intrahepatic component amenable to radiofrequency ablation (RFA).
• Patients must have disease that is not amenable to potentially curative resection, transplantation or ablation. For Cohorts A, C and D patients must have progressed on, been intolerant to, or refused prior sorafenib therapy. Cohort E patients must have received at least one line of chemotherapy for BTC.
• Disease must be technically amenable to transhepatic arterial chemoembolization (TACE), radiofrequency ablation (RFA) or cryoablation. Each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology. Patients must have evaluable disease.
• If liver cirrhosis is present, patient must have a Child-Pugh A/B7 classification.
• Age greater than or equal to 18 years
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must have normal organ and marrow function as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,000/mcL
• platelets greater than or equal to 60,000/mcL
• total bilirubin, If cirrhosis present: Part of Child Pugh requirement. If no cirrhosis: Bili should be less than or equal to 2 times upper limit of normal (ULN)
• Serum albumin, If cirrhosis present: Part of Child Pugh requirement. If no cirrhosis: albumin should be greater than or equal to 2.5g/dl
• Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5 times ULN.
• creatinine, less than 1.5 times institution upper limit of normal OR

You may not qualify if:

• 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.
• 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.
• 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.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• \. 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.
• \. History of hypersensitivity reaction to human or mouse antibody products.
• \. Patients with unhealed surgical wounds for more than 30 days.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (7)

• 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.

  PMID: 11668491 BACKGROUND

• 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.

  PMID: 18477802 BACKGROUND

• 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.

  PMID: 20818862 BACKGROUND

• 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.

  PMID: 30578687 RESULT

• 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.

  PMID: 30688989 RESULT

• 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.

  PMID: 27816492 RESULT

• 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.

  PMID: 28923358 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Biliary Tract Neoplasms; Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

tremelimumab; Radiofrequency Ablation; Cryosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Tim F. Greten
• Organization: National Cancer Institute

tim.greten@nih.gov

(301) 451-4723

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: May 15, 2013
• Study Start: May 2, 2013
• Primary Completion: June 7, 2017
• Study Completion: June 7, 2017
• Last Updated: December 10, 2019
• Results First Posted: December 10, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)