Clinical Trial 18924

Cancer Type:
Interventions:BAY 43-9006 (Sorafenib); Bavituximab (Tarvacin); Sorafenib

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Jessica Frakes

Overview

Study Title

A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for 1st Line Treatment of Unresectable Hepatocellular Carcinoma

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.

Objective

Primary Objective: To determine the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) (or the highest protocol-defined dose level in the absence of establishing an MTD) of SBRT as part of a combination with sorafenib and bavituximab in patients with multifocal, unresectable HCC. Secondary Objectives: 1. To determine tumor response to the combination. 2. To determine progression free survival following SBRT and sorafenib/bavituximab. 3. To determine overall survival following SBRT and sorafenib/bavituximab. Exploratory Objectives: 1. To correlate radiosensitivity index (RSI) with therapeutic response. 2. To correlate a 12-gene chemokine signature with therapeutic response. 3. To correlate plasma levels of circulating cytokines with therapeutic response. 4. To measure beta2-GP1 and PS-exosome levels.

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