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Trial record 1 of 1 for:    NCT02560779
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Trial of TRC105 and Sorafenib in Patients With HCC

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Tracon Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT02560779
First received: September 10, 2015
Last updated: January 20, 2016
Last verified: January 2016
  Purpose

The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose sorafenib in patients with hepatocellular carcinoma. Up to 18 patients will be treated.

The purpose of the phase 2 portion is to estimate the ORR of patients with hepatocellular carcinoma by RECIST 1.1. Up to 21 patients will be treated in phase 2.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: TRC105
Drug: Sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Phase 1B/2 Trial of TRC105 and Sorafenib in Patients With Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:


Further study details as provided by Tracon Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose of TRC105 in Combination with Sorafenib (Phase 1b). [ Time Frame: 4 months ]

Secondary Outcome Measures:
  • Preliminary evidence of antitumor activity when TRC105 is added to sorafenib will be assessed by Overall Response Rate (ORR). (Phase 1b) [ Time Frame: 4 months ]
  • Preliminary evidence of antitumor activity when TRC105 is added to sorafenib will be assessed by Progression-Free Survival (PFS). (Phase 1b) [ Time Frame: 4 months ]
  • Pharmacokinetic profile of TRC105 and sorafenib when given together (Phase 1b and Phase 2) [ Time Frame: 19 months ]
    Peak Plasma Concentration (Cmax)

  • TRC105 immunogenicity as assessed by Anti-Product Antibody (APA). (Phase 1b and Phase 2) [ Time Frame: 19 months ]
  • Changes in circulating angiogenic biomarkers following treatment with TRC105 and sorafenib. (Phase 1b and Phase 2) [ Time Frame: 19 months ]
  • Frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03). (Phase 1b and Phase 2) [ Time Frame: 19 months ]

Estimated Enrollment: 39
Study Start Date: January 2016
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 and Sorafenib
Bi-weekly TRC105 in combination with standard dose Sorafenib.
Drug: TRC105
Bi-weekly TRC105 will be given with standard-dose sorafenib.
Other Name: Chimeric Antibody (TRC105) to CD105
Drug: Sorafenib
Bi-weekly TRC105 will be given with standard-dose sorafenib.
Other Name: Nexavar

Detailed Description:
Sorafenib is an oral multikinase inhibitor targeting several receptor tyrosine kinases, including the VEGF receptor (VEGFR), implicated in pathologic angiogenesis, tumor growth, and cancer progression. Sorafenib is approved for the treatment of unresectable hepatocellular carcinoma (HCC). TRC105 is an antibody to endoglin, an important angiogenic target on proliferating endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR in preclinical models. Together, the use of TRC105 with sorafenib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with sorafenib alone.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.
  2. Patients must have disease that is not amenable to potentially curative resection or ablative techniques or that has recurred following ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE) or must have progressed on TACE. Patients must not be candidates for liver transplantation.
  3. If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification.
  4. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
  5. Measurable disease by RECIST 1.1 (Phase 2 only)
  6. Age of 18 years or older
  7. ECOG performance status ≤ 1
  8. Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
  9. Adequate organ function
  10. Willingness and ability to consent to participate in study
  11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
  12. Men who are sterile OR agree to use at least two forms of a reliable and highly effective method of birth control and to not donate sperm and for at least 180 days following last dose of TRC105 or sorafenib.
  13. Woman of non-child bearing potential due to surgical sterilization confirmed by medical history or menopause, OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 forms of a reliable and highly effective method of birth control during the study and for at least 180 days after stopping TRC105 or sorafenib.

Exclusion Criteria:

  1. Prior anticancer systemic therapy
  2. Current treatment on another therapeutic clinical trial
  3. Prior radiation therapy within 28 days of starting the study treatment
  4. No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure.
  5. Proteinuria
  6. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy.
  7. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
  8. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.
  9. Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.
  10. Thrombolytic use within 10 days prior to first day of study therapy
  11. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
  12. Need for anticoagulation
  13. History of liver transplant
  14. History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.
  15. History of peptic ulcer disease within 3 months of treatment.
  16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  17. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
  18. Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.
  19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02560779

Contacts
Contact: Clinical Trials Information Clinicaltrials@traconpharma.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Carol Rose, CCRC    626-218-9382    crose@coh.org   
Principal Investigator: Joseph Chao, MD         
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
Investigators
Study Director: Charles Theuer, MD, PhD Tracon Pharmaceuticals Inc.
  More Information

Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02560779     History of Changes
Other Study ID Numbers: 105HCC101
Study First Received: September 10, 2015
Last Updated: January 20, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Tracon Pharmaceuticals Inc.:
TRC105
CD105
Endoglin
Angiogenesis inhibitor
HCC
TKI
Tyrosine Kinase Inhibitor
Sorafenib
Nexavar

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Niacinamide
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Immunologic Factors

ClinicalTrials.gov processed this record on March 24, 2017