Sorafenib and Bavituximab Plus SBRT in Unresectable Hepatocellular Carcinoma

NCT ID: NCT02989870

Last Updated: 2020-06-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-27
• Study Completion Date: 2018-10-15

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SBRT, Sorafenib and Bavituximab

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.

Group Type: EXPERIMENTAL

Stereotactic Body Radiation Therapy (SBRT)

Intervention Type: 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.

Sorafenib

Intervention Type: DRUG

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

Bavituximab

Intervention Type: DRUG

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

Interventions

Stereotactic Body Radiation Therapy (SBRT)

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.

Intervention Type: RADIATION

Sorafenib

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

Intervention Type: DRUG

Bavituximab

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

Intervention Type: DRUG

Other Intervention Names

radiotherapy; Nexavar; Kinase inhibitor; Immunotherapy

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Anti-coagulant therapy, bleeding or clotting disorder
• Symptomatic metastatic brain or meningeal tumors
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• History of organ allograft (including corneal transplant)
• Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
• Women who are pregnant or breast-feeding
• Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Frakes, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

MCC-18924

Identifier Type: -

Identifier Source: org_study_id