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Hepatocellular CarcinomaPhase 2NCT01375569

TRC105 for Liver Cancer That Has Not Responded to Sorafenib

A Phase 2 study testing TRC105 in people with Hepatocellular Carcinoma and Hepatocellular Cancer, 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: 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
TRC105
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
22 Jun 2011to 1 Dec 2015
Phase
Phase 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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
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  • 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
  • Creatinine less than or equal to 1.5 times upper normal limits OR creatinine clearance greater than or equal to 40 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal, as calculated by the Cockcroft Gault formula.
  • Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.
  • Patients must not have other invasive malignancies within the past 3 years (with the exception of non-melanoma skin cancers, carcinoma in situ of the cervix and noninvasive bladder cancer).
  • 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.
  • Patient must be able to understand and willing to sign a written informed consent document.
  • -Men and women of all races and ethnic groups are eligible for this trial.

Who cannot join

  • 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.
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  • 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).
  • Pregnancy and breast feeding are exclusion factors. 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.

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 Phase II Study of TRC105 in Patients With Hepatocellular Carcinoma (HCC) Who Have Progressed on Sorafenib

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.
Read more

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.
Read the detailed description

Background:

  • Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. The Study of Heart and Renal Protection (SHARP) study established Sorafenib as a standard consideration in this disease and set the bar for future studies of systemic therapy. There is no standard therapy for patients whose disease has progressed despite Sorafenib therapy.
  • TRC105 is a chimeric, anti-angiogenic monoclonal antibody that binds CD105, a transmembrane receptor overexpressed by proliferating endothelial cells. TRC105 binds to CD105-expressing endothelial cells and mediates growth inhibition, apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC).

Objectives:

Primary:

-To evaluate time to tumor progression (TTP) for TRC105 in HCC.

Secondary:

  • To evaluate safety of TRC105 in HCC.
  • To evaluate the immunogenicity of TRC105 as measured by human antichimeric antibody (HACA) and human antimouse antibody formation.
  • To evaluate anti-tumor response as determined by standard and European Association for the Study of the Liver (EASL) -modified Response Evaluation Criteria in Solid Tumors (RECIST) response criteria.
  • To perform correlative studies assessing potential biomarkers of response to TRC105.

Eligibility:

  • Histologically or cytologically confirmed diagnosis of HCC.
  • Childs-Pugh A or B (7 points) cirrhosis only is allowed.
  • Patients must have disease that is not amenable to potentially curative resection.
  • Patients must have progressed on or been intolerant of prior sorafenib therapy.
  • No history of bleeding varices (unless subsequent liver transplant). All patients must have had endoscopic evaluation within 6 months of starting study.
  • No history of bleeding varices in previous 1 year (unless subsequent liver transplant). No anti-coagulation (except low-dose aspirin).

Design:

  • This is a single-arm phase II study of TRC105 in patients with HCC.
  • TRC105 will be administered as an intravenous infusion every two weeks. Patients will be re-staged every 8 weeks.
  • The primary endpoint of the study will be Time to Tumor Progression (TTP). The primary purpose of this study is to evaluate the ability of TRC105 as a second line treatment to improve upon the time to progression (TTP) of patients with refractory HCC.
Being tested
TRC105
Keywords
CD105, Monoclonal Antibody, Anti-Angiogenic, Chimeric, Apoptosis, Liver Cancer
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

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

  • TRC105Drug

Study groups in NCT01375569
Study groupRoleWhat they receive
TRC105 in Liver CancerExperimentalTRC105 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.
Receives: Drug: TRC105

What is being measured

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

  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).

    Measured: 2 years

Secondary outcomes (1)

  1. Count of Participants With Adverse Events

    here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    Measured: 25 months, 15 days

Timeline

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

  1. First posted17 Jun 2011 (estimated)
  2. Study start22 Jun 2011
  3. Primary completion1 Feb 2014
  4. Study completion1 Dec 2015

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01375569
Sponsor's protocol ID
110181
Other IDs
11-C-0181
Status last verified
Jun 2017
First submitted
16 Jun 2011
Last updated
28 Jul 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

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

  • 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.

    PubMed 14581446

  • 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.

    PubMed 18650514

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TRC105 in people with Hepatocellular Carcinoma and Hepatocellular Cancer, 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 22 inclusion and 15 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 28 Jul 2017. 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 phase mean?

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 17 Mar 2015). 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?

Time to Tumor Progression (TTP) for TRC105 in Hepatocellular Carcinoma (HCC). (time frame: 2 years). 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 NCT01375569, which also lists 3 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 28 Jul 2017.

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