- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02560779
Trial of TRC105 and Sorafenib in Patients With HCC
An Open Label Phase 1B/2 Trial of TRC105 and Sorafenib in Patients With Hepatocellular Carcinoma (HCC)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Alabama
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Birmingham, Alabama, United States, 35294-3300
- University of Alabama
-
-
Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals
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Texas
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Houston, Texas, United States, 77030-4009
- MD Anderson
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration
- Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
- Ascites or pleural effusion requiring intervention or that required intervention within the last month and has recurred
- Pericardial effusion (except trace effusion identified by echocardiogram)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Carotuximab (TRC105) and Sorafenib
Carotuximab (TRC105) in combination with standard dose Sorafenib.
|
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.
Other Names:
400 mg of sorafenib will be given twice daily.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Who Experience Dose Limiting Toxicities by Dose Level
Time Frame: 4 months
|
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.
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4 months
|
Overall Response Rate (ORR)
Time Frame: 4 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic Profile of TRC105 When Given With Sorafenib
Time Frame: 5 weeks
|
Steady state mean trough serum concentrations by dose level of TRC105 after 5 weeks of dosing were measured using validated methods after 5 weeks of dosing.
|
5 weeks
|
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA)
Time Frame: 19 months
|
Number of patients who tested positive for antibodies to TRC105 by dose level.
Anti-Product Antibody (APA) concentrations were measured using validated ELISA methods.
|
19 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Sorafenib
Other Study ID Numbers
- 105HCC101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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