Study of Bavituximab and Sorafenib In Patients With Advanced Liver Cancer

NCT01264705 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: STU 062010-150
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open-label, single-institution phase I/II therapeutic trial of bavituximab and sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study will be activated at the UT Southwestern Medical Center, comprised of The Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Hospitals-St. Paul and Parkland Memorial Hospital System. Advanced HCC is defined as disease that is not amenable to surgical resection or orthotopic liver transplantation or is metastatic in nature.

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

Cirrhosis; GI Cancer; Hepatitis; Oncology

Outcome Measures

Primary Outcomes (2)

• Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up.

  Median radiographic time to progression (TTP) was calculated from treatment initiation to first evidence of disease progression or last follow-up by using the Kaplan-Meier method. The 95% confidence intervals (CIs) for time-to-progression data was calculated using Greenwood's formula.

  Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months

• Number of Patients With Dose Limiting Toxicity

  Dose limiting toxicity by serious adverse events by CTCAE version 4.0

  8 months.

Secondary Outcomes (3)

• Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater.

  Up to 3 months of patient enrollment (phase 1)

• Median Months of Overall Survival Calculated From Treatment Initiation to Death or Last Follow-up.

  Treatment initiation to death or last follow-up, an average 24 months

• Median Months of Disease Specific Survival Calculated From Treatment Initiation to Death From Advanced HCC (Hepatocellular Carcinoma) or Last Follow-up.

  Treatment initiation to first evidence of death from advanced liver cancer or last follow-up, an average of 12 months

Study Arms (3)

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

EXPERIMENTAL

Cohort 1: Participants were administered Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Drug: bavituximab (0.3 mg/kg) and sorafenib

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

EXPERIMENTAL

Cohort 2: Participants were administered Bavituximab:1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Drug: bavituximab (1.0 mg/kg ) and sorafenib

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

EXPERIMENTAL

Cohort 3: Participants were administered Bavituximab:3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Drug: bavituximab (3.0 mg/kg) and sorafenib

Interventions

bavituximab (0.3 mg/kg) and sorafenib DRUG

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

bavituximab (1.0 mg/kg ) and sorafenib DRUG

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

bavituximab (3.0 mg/kg) and sorafenib DRUG

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

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 a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
• Histologically confirmed.
• MRI or CT consistent with liver cirrhosis and at least one solid liver lesion \>2 cm with early enhancement and delayed enhancement washout regardless of AFP.
• AFP \>400 ng/ml and evidence of at least one solid liver lesion \>2 cm regardless of specific imaging characteristics on CT or MRI.
• Locally advanced or metastatic disease.
• Patients with locally advanced disease must have disease deemed to be unresectable or not eligible for hepatic transplantation. Determination will occur in the weekly GI DMT meeting by surgical oncologists and transplant surgeons.
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension (longest diameter to be measured) according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at least 2 cm with conventional techniques or at least 1 cm with spiral computed tomography.
• Child-Pugh Score A.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
• Absolute neutrophil count ≥ 1,500 cells/mm3.
• Platelet count ≥ 75,000 cells/mm3.
• Total bilirubin ≤ 3.0 mg/dl.
• Hemoglobin ≥ 8.5 g/dl.
• AST and ALT ≤ 5.0 times upper limit of normal.

You may not qualify if:

• History of bleeding diathesis or coagulopathy.
• Symptomatic or clinically active brain metastases.
• Major surgery within previous 4 weeks.
• History of thromboembolic events (including both pulmonary embolisms and deep vein thrombosis); central venous catheter-related thrombosis \> 6 months prior is allowed.
• Prior adjuvant therapy with sorafenib or other Raf/MEK/RAS or VEGFR inhibitors. Prior adjuvant therapy is allowed provided it was completed \> 6 months ago and there is documented recurrence of hepatocellular carcinoma.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Mokdad AA, Zhu H, Beg MS, Arriaga Y, Dowell JE, Singal AG, Yopp AC. Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial. Target Oncol. 2019 Oct;14(5):541-550. doi: 10.1007/s11523-019-00663-3.

  PMID: 31429027 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Fibrosis; Gastrointestinal Neoplasms; Hepatitis; Neoplasms

Interventions

bavituximab; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal 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

Results Point of Contact

• Title: Adam Yopp, MD
• Organization: UT Southwestern Medical Center

adam.yopp@utsouthwestern.edu

214-648-5870

Study Officials

• Adam C Yopp, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 22, 2010
• Study Start: January 1, 2011
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: November 12, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-10

Locations

US (1)