Tremelimumab With Chemoembolization or Ablation for Liver Cancer

Phase 1

Completed

Conditions: Biliary Tract Neoplasms
Liver Cancer
Hepatocellular Carcinoma
Biliary Cancer
Heptocellular Cancer

Interventions: Drug: Tremelimumab
Procedure: RFA
Procedure: TACE
Procedure: Cryoablation

Registration Number: NCT01853618

Lead Sponsor: National Cancer Institute (NCI)

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Pilot 1/Arm A1-Tremelimumab + RFA or TACE	Tremelimumab	Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
3/Arm B - Tremelimumab + TACE	Tremelimumab	Tremelimumab + Transarterial Catheter Chemoembolization (TACE)
Pilot 1/Arm A1-Tremelimumab + RFA or TACE	RFA	Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
Pilot 1/Arm A1-Tremelimumab + RFA or TACE	TACE	Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
2/Arm A2 - Tremelimumab + RFA or TACE	Tremelimumab	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
2/Arm A2 - Tremelimumab + RFA or TACE	RFA	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
2/Arm A2 - Tremelimumab + RFA or TACE	TACE	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
3/Arm B - Tremelimumab + TACE	TACE	Tremelimumab + Transarterial Catheter Chemoembolization (TACE)
4/Arm C (never opened)	Tremelimumab	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
4/Arm C (never opened)	TACE	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
4/Arm C (never opened)	Cryoablation	Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)
5/Arm D - Tremelimumab + Cryoablation	Tremelimumab	Tremelimumab + Cryoablation
5/Arm D - Tremelimumab + Cryoablation	Cryoablation	Tremelimumab + Cryoablation
6/Arm E - Tremelimumab + RFA	Tremelimumab	Tremelimumab + Radiofrequency Ablation (RFA)
6/Arm E - Tremelimumab + RFA	RFA	Tremelimumab + Radiofrequency Ablation (RFA)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Serious and Non-Serious Adverse Events Regardless of Attribution	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.	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.

Secondary Outcome Measures

Name	Time	Method
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	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 (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	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	From the time of initial treatment consent until date of death for each patient. Overall survival ranged from 6 months to 13.1 months.	Overall survival is defined as the amount of time a subject survives after therapy.