Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Biliary Tract Neoplasms

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Biliary Tract Diseases

Biliary Tract Cancer

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Chlorotrianisene

Liver Extracts

Tremelimumab

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

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

Tremelimumab + Transarterial Catheter Chemoembolization (TACE)

Tremelimumab + Radiofrequency Ablation (RFA)

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

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)

TACE

Cryoablation

Tim F Greten, M.D.

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.

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.

Tremelimumab With Chemoembolization or Ablation for Liver Cancer

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)

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.

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.

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.

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

National Cancer Institute (NCI)

Principal Investigator

All deaths in the mortality module are attributable to progressive disease (all deaths that occurred are reported).

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

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

RFA: Performed on Day 36

TACE: 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)

Pilot 1/Arm A1-Tremelimumab + RFA or TACE

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

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

RFA: Performed on Day 36

TACE: 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)

2/Arm A2 -Tremelimumab + RFA or TACE

Tremelimumab + Transarterial Catheter Chemoembolization (TACE)

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

TACE: 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)

3/Arm B - Tremelimumab + TACE

Tremelimumab + Cryoablation

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

Cryoablation: Performed on Day 36

5/Arm D - Tremelimumab + Cryoablation

Tremelimumab + Radiofrequency Ablation (RFA)

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

RFA: Performed on Day 36

6/Arm E - Tremelimumab + RFA

2/Arm A2 - Tremelimumab + RFA or TACE

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Any surgical resection

Any TACE

Any chemotherapy

Any radiation therapy

Misc. therapy - Y90

Misc. therapy - Hyperthermia

Transarterial catheter chemoembolization (TACE)

Previous Therapy

Dr. Tim F. Greten

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

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Tremelimumab + Radiofrequency Ablation (RFA)

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

RFA: Performed on Day 36

Spots Global Cancer Trial Database for blocking of immune suppression