Sorafenib and Bavituximab Plus SBRT in Unresectable Hepatocellular Carcinoma

NCT02989870 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: MCC-18924
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves a course of radiation to up to 5 tumors in the participant's liver followed by systemic therapy. (Treatment using substances that travel through the bloodstream, reaching and affecting cells all over the body.) The type of radiation is called stereotactic body radiation therapy (SBRT). The purpose of this study is to compare the effects, good and/or bad, of different doses of SBRT given along with the systemic therapies, sorafenib and bavituximab. The researchers want to see which dose of radiation will work best in stimulating the immune response and provide local control to the participant's liver. The usual treatment for hepatocellular carcinoma that is unresectable can be transarterial therapy, sorafenib alone and/or clinical trial.

Conditions

HepatoCellular Carcinoma; Unresectable HepatoCellular Carcinoma; Liver Cancer

Keywords

Liver Disease; Child-Pugh Class A; Child-Pugh Class B7

Outcome Measures

Primary Outcomes (1)

• Occurrence of Treatment Related Adverse Events

  Safety and tolerability, as assessed by presence of adverse events, serious adverse events, dose limiting toxicity (DLTs), abnormal laboratory parameters, vital signs. A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation, which occurs from the start of radiation up to 42 days and is considered by the Investigators to be definitely, probably, or possibly related to the treatment. A DLT will be defined as any Grade 3 or higher treatment-related toxicity that occurs during the DLT evaluation period.

  From beginning of treatment to 30 days post-treatment, approximately 2 years

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 24 months post treatment

• Progression Free Survival (PFS)

  Up to 24 months post treatment

• Overall Survival (OS)

  Up to 24 months post treatment

Study Arms (1)

SBRT, Sorafenib and Bavituximab

EXPERIMENTAL

This will be a 3+3 design with 3 dose cohorts. Following the dose escalation phase, an additional 6 patients will be enrolled as part of the dose expansion cohort.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Sorafenib; Drug: Bavituximab

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Participants will receive 3-5 fractions of radiation as determined by the dose level at time of enrollment. The starting dose level will be Dose Level 1: 8 Gy x 3 fractions for a total of 24 Gy. If sufficient treatment related toxicity is observed at the "initial starting dose", then the dose will be reduced to 16 Gy in 2 fractions of 8 Gy. The dose per fraction for each participant will be provided at the time of registration based on the toxicity experience of the previous participants on study. This will be escalated to 40 Gy in 5 fractions of 8 Gy.

Also known as: radiotherapy

SBRT, Sorafenib and Bavituximab

Sorafenib DRUG

Sorafenib by mouth (PO): 200 mg twice a day (BID) then 400 mg BID.

Also known as: Nexavar, Kinase inhibitor

SBRT, Sorafenib and Bavituximab

Bavituximab DRUG

Bavituximab intravenously (IV): 3 mg/kg every week (q wk).

Also known as: Immunotherapy

SBRT, Sorafenib and Bavituximab

Eligibility Criteria

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

You may qualify if:

• Advanced, unresectable hepatocellular carcinoma (unsuitable for resection, transplant or ablation)
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Must have normal organ and marrow function
• Childs-Pugh score of A or B7
• Must have measurable/evaluable disease as per RECIST 1.1 criteria
• Females of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both males and females, effective methods of contraception must be used throughout the study and for four months following the last dose.
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Must be able to understand and be willing to sign the written informed consent form
• No more than 10 lesions in the liver

You may not qualify if:

• Have received radiation therapy, major surgery, other locoregional therapy, within 4 weeks prior to the first date of SBRT
• Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
• Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time
• Any one hepatocellular carcinoma \> 15 cm
• Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC \> 20 cm
• Direct tumor extension into the stomach, duodenum, small bowel or large bowel
• Measureable common or main branch biliary duct involvement with HCC
• Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 3.0 cm, in sum of maximal diameters (e.g., presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions). Note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is \> 2.0 cm.
• Use of regular phenytoin, carbamazepine, hypericum perforatum \[also known as St. John's wort\] or rifampin
• Have received sorafenib or other systemic therapies for treatment of HCC in the past.
• Active autoimmune disease; Patients with type I diabetes mellitus, hypothyroidism requiring only hormone replacement, psoriasis not requiring systemic treatment, or vitiligo are permitted for enrollment.
• No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before the trial are allowed.
• Myocardial infarction within past 6 months, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia
• Congenital long QT syndrome
• Previous stroke within past 12 months

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Liver Diseases

Interventions

Radiosurgery; Radiotherapy; Sorafenib; bavituximab; Immunotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; 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; Immunomodulation; Biological Therapy

Study Officials

• Jessica Frakes, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 8, 2016
• First Posted: December 12, 2016
• Study Start: March 27, 2017
• Primary Completion: October 15, 2018
• Study Completion: October 15, 2018
• Last Updated: June 5, 2020

Record last verified: 2020-06

Locations

US (1)