Trial of TRC105 and Sorafenib in Patients With HCC

NCT02560779 | Completed Phase 1 Results

• 1 other identifier: 105HCC101
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

TRC105; CD105; Endoglin; Angiogenesis inhibitor; HCC; TKI; Tyrosine Kinase Inhibitor; Sorafenib; Nexavar

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who Experience Dose Limiting Toxicities by Dose Level

  If 1 of 3 patients experienced a DLT, the dose level was expanded to 6 patients. The maximum tolerated dose (MTD) would have been exceeded if ≥ 33% of patients experience DLT at a given dose level. DLT occurred when a patient had 1 or more toxicities outlined in the protocol that was considered at least possibly related to TRC105 during the first 4 months of participation in the trial. The number of DLTs by dose cohort have been presented.

  4 months

• Overall Response Rate (ORR)

  Number of patients with a response (PR or CR) are included by dose level. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients must have had a screening scan and at least 1 on study scan to be eligible for RECIST 1.1 evaluation.

  4 months

Secondary Outcomes (2)

• Pharmacokinetic Profile of TRC105 When Given With Sorafenib

  5 weeks

• TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA)

  19 months

Study Arms (1)

Carotuximab (TRC105) and Sorafenib

EXPERIMENTAL

Carotuximab (TRC105) in combination with standard dose Sorafenib.

Drug: Carotuximab (TRC105); Drug: Sorafenib

Interventions

Carotuximab (TRC105) DRUG

Bi-weekly iv TRC105 (15 mg/kg) will be given with 400mg sorafenib twice daily in the phase 1B portion of the study. Weekly iv TRC105 (10 mg/kg) will be given with 400mg sorafenib twice daily in the phase 2 portion of the study.

Also known as: Chimeric Antibody (TRC105) to CD105

Carotuximab (TRC105) and Sorafenib

Sorafenib DRUG

400 mg of sorafenib will be given twice daily.

Also known as: Nexavar

Carotuximab (TRC105) and Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.
• 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.
• If liver cirrhosis is present, patient must have a Child-Pugh A or B (7 points) classification.
• 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.
• Measurable disease by RECIST 1.1 (Phase 2 only)
• Age of 18 years or older
• ECOG performance status ≤ 1
• Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
• Adequate organ function
• Willingness and ability to consent to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• 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.
• 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.

You may not qualify if:

• Prior anticancer systemic therapy
• Current treatment on another therapeutic clinical trial
• Prior radiation therapy within 28 days of starting the study treatment
• No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure.
• Proteinuria
• Uncontrolled chronic hypertension defined as systolic \> 150 or diastolic \> 90 despite optimal therapy.
• History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months.
• Active bleeding or pathologic condition that carries a high risk of bleeding. No bleeding diathesis.
• Thrombolytic use within 10 days prior to first day of study therapy
• History of hemorrhage or hemoptysis (\> ½ teaspoon bright red blood) within 3 months of starting study treatment
• Need for anticoagulation
• History of liver transplant
• History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.
• History of peptic ulcer disease within 3 months of treatment.

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (3)

University of Alabama

Birmingham, Alabama, 35294-3300, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

MD Anderson

Houston, Texas, 77030-4009, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

carotuximab; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

TRC105 development has been discontinued due to lack of efficacy. Secondary endpoints including PFS, OS, duration of response, sorafenib PK, circulating angiogenic biomarkers and assessment of IGF-1-modified Child-Pugh score were not performed.

Results Point of Contact

• Title: Charles Theuer
• Organization: TRACON Pharmaceuticals Inc.

ctheuer@traconpharma.com

(858) 550-0780

Study Officials

• Charles Theuer, MD, PhD

  Tracon Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: September 25, 2015
• Study Start: November 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: July 17, 2020
• Results First Posted: July 17, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)