TRC105 for Liver Cancer That Has Not Responded to Sorafenib

NCT01375569 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 11018111-C-0181
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- TRC105 is an experimental cancer drug. It is designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. People with hepatocellular carcinoma (or liver cancer) sometimes do not respond to standard treatments. This includes the cancer drug sorafenib. Objectives: \- To test the safety and effectiveness of TRC105 to treat liver cancer that has not responded to standard therapy. Eligibility:

• People at least 18 years of age who have hepatocellular carcinoma (or liver cancer) that has not responded to standard therapy. Participants also will not be eligible for a liver transplant.
• No anticoagulation therapy is allowed with the exception of low-dose aspirin.
• No history of bleeding disorders, peptic ulcer disease or gastritis. Design:
• Participants will have a physical exam and medical history. They will also have blood and urine tests, and imaging studies.
• Participants will receive TRC105 once a week. They will also have two daily doses of a steroid the day before each treatment. This will help prevent known side effects.
• Participants will be monitored with blood and urine tests. They will also have imaging studies every two months to study the effect of the drug on tumor growth.
• Participants will continue to have TRC105 as long as they do not have severe side effects and their liver cancer stops growing or shrinks. After stopping TRC105, they will have yearly visits with physical exams and blood tests.

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer; Carcinoma, Hepatocellular

Keywords

CD105; Monoclonal Antibody; Anti-Angiogenic; Chimeric; Apoptosis; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Tumor Progression (TTP) for TRC105 in Hepatocellular Carcinoma (HCC).

  Time to tumor progression is defined as the proportion of participants who are progression free after 4 months on study. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions).

  2 years

Secondary Outcomes (1)

• Count of Participants With Adverse Events

  25 months, 15 days

Study Arms (1)

TRC105 in Liver Cancer

EXPERIMENTAL

TRC105 is an experimental cancer drug designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. This drug is being used to test the safety and effectiveness to treat liver cancer that has not responded to standard therapy. TRC105 will be given as an intravenous infusion every two weeks.

Drug: TRC105

Interventions

TRC105 DRUG

TRC105 in Liver Cancer

Eligibility Criteria

• Age: 18 Years - 80 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) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study.
• 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.
• Patients must have disease that is not amenable to potentially curative resection or ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE). Patients may have had prior TACE and had disease progression following it. Patients must not be considered potential candidates for liver transplantation. This determination will be made after hepatobiliary surgical input at the NCI multidisciplinary conference.
• All patients enrolled will be required to have measurable disease.
• If liver cirrhosis is present, patient must have a Child-Pugh A classification.
• Patients must have progressed on or been intolerant of prior sorafenib therapy.
• Patients must with cirrhosis have had esophagogastric endoscopy within the previous 6 months prior to study entry for the assessment of varices. If the patient has not had this done they must be willing to undergo this procedure prior to study entry.
• 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:
• Absolute neutrophil count greater than or equal to 1,500/mcL
• Platelets greater than or equal to 60,000/mcL
• Total bilirubin less than or equal to 3 times upper normal limits
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 10 times upper limit of normal

You may not qualify if:

• Patients who have had chemotherapy, large field radiotherapy, or major surgery must wait 4 weeks prior to entering the study (2 weeks is sufficient for targeted systemic therapy provided toxicity has recovered to less than or equal to grade 1).
• Patients may not be receiving any anti-cancer agents not approved by the Food and Drug Administration (FDA) within the past 4 weeks.
• 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.
• Proteinuria, as demonstrated by a 24 hour protein of greater than or equal to 2000 mg. Urine protein will be screened by urine protein-creatinine ratio (UPC). For urine protein-to-creatinine (UPC) ratio \> 1.0, a 24-hour urine protein will need to be obtained and the level should be \< 2000 mg for patient enrollment.
• Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic blood pressure (BP) 160, diastolic BP \> 100), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• No anti-coagulation therapy is allowed with the exception of low-dose aspirin.
• No bleeding diathesis.
• Patients with a history of bleeding varices in previous 1 year are excluded (unless patient has subsequently had a liver transplant). Those with gastric varices or varices that are deemed as high risk by the endoscopist should be placed on appropriate medical therapy as advised by the gastroenterologist.
• History of peptic ulcer disease or hemorrhagic gastritis within 6 months of TRC105 administration, unless patient has received adequate treatment for peptic ulcer disease or hemorrhagic gastritis and has evidence of complete resolution documented by esophagogastroduodenoscopy (EGD). Mild gastritis is allowed.
• Corrected QT interval (QTc) \> 500 msec.
• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and TRC105. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that TRC105 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to TRC105.
• History of hypersensitivity reaction to human or mouse antibody products.
• Patients with a history of familial bleeding disorders.
• Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).
• Men and women of all races and ethnic groups are eligible for this trial.

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 (3)

• 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

• Yoo HY, Patt CH, Geschwind JF, Thuluvath PJ. The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time. J Clin Oncol. 2003 Dec 1;21(23):4329-35. doi: 10.1200/JCO.2003.11.137. Epub 2003 Oct 27.

  PMID: 14581446 BACKGROUND

• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

  PMID: 18650514 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

carotuximab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

gretentf@mail.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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 17, 2011
• Study Start: June 22, 2011
• Primary Completion: February 1, 2014
• Study Completion: December 1, 2015
• Last Updated: July 28, 2017
• Results First Posted: March 17, 2015

Record last verified: 2017-06

Locations

US (1)