Trial snapshot
- Formal name: ANGIO-A: Safety and Tolerability of Oral Cyclophosphamide and Sorafenib with Intravenous Bevacizumab with the Addition of Atezolizumab in Pediatric Solid Tumor Patients
- Trial type: Includes fibrolamellar carcinoma
- Phase: Phase I / II
- Recruitment status: Active, Recruiting
- Eligible ages: less than 30 years old at time of enrollment
- Location: Memphis, TN (St. Jude Children’s Research Hospital)
- ClinicalTrials.gov ID: NCT05468359
Background and overview
Cancer is more than a collection of abnormal cancer cells. Tumors create an environment around themselves that helps them survive and grow. This environment includes blood vessels that supply oxygen and nutrients, as well as signals that can prevent the immune system from recognizing and attacking the cancer.
This Phase I/II clinical trial, led by pediatric oncologist Dr. Jess Gartrell at St. Jude Children’s Research Hospital in Memphis, Tennessee, is testing a treatment approach designed to disrupt these tumor-supporting systems. The study is focused primarily on hepatocellular carcinoma, fibrolamellar carcinoma, desmoplastic small round cell tumors, and malignant rhabdoid tumors in children, adolescents, and young adults.
The trial combines medicines that attack cancer from two directions:
- Disrupting “tumor angiogenesis,” the formation of blood vessels that help tumors grow
Tumors need a steady supply of oxygen and nutrients to survive. They create their own network of blood vessels to deliver these resources. Several drugs in ANGIO-A are designed to disrupt that process.
- Helping the immune system recognize and attack cancer
Cancer cells can sometimes hide from the immune system by sending signals that tell immune cells not to attack. ANGIO-A includes an immunotherapy drug that turns off an “immune checkpoint” which cancer cells often exploit to avoid being killed by immune cells that penetrate tumors.
Image credit: Mjeltsch, via Wikimedia Commons, licensed under CC BY-SA 4.0
Specific drug combination
The ANGIO-A trial combines four drugs that work in different ways:
- Bevacizumab (Avastin®) helps block signals that tumors use to grow new blood vessels.
- Sorafenib (Nexavar®) blocks several signals that tumors use to build and maintain blood vessels, including the VEGF pathway. By interfering with these signals, it may make it harder for the tumor to support its own growth. This drug was chosen in preference to some related medicines (including lenvatinib, regorafenib, and cabozantinib) because the amount of Sorafenib in an individual’s blood can be measured accurately over time, which enables the drug dose to be specifically adjusted for each patient to maintain an effective level (referred to as “PK-guided sorafenib”)
- Cyclophosphamide (Cytoxan®) is given at a low dose and may help damage rapidly dividing cells involved in building tumor blood vessels.
- Atezolizumab (Tecentriq®) is an immune checkpoint inhibitor (ICI) which blocks cancer cells from conveying a “stop, don’t kill me” braking signal to anticancer immune cells.
Researchers have learned that simply blocking blood vessel growth is usually not enough to eliminate a cancer. At the same time, immunotherapies often work better when immune cells can effectively reach tumors. ANGIO-A was developed to address both challenges at once — improve conditions for an immune response while also making it harder for the tumor to grow and protect itself.
What are researchers hoping to learn?
The study will evaluate whether combining these four medicines is safe and whether this strategy can help patients with FLC and other solid tumors. Researchers hope that improving blood vessel function while strengthening the immune response may provide a more effective way to control cancer than either approach alone.
Trial details and eligibility
This trial has two parts:
- Part 1: Safety Study (Phase I)
Researchers first enroll patients with various relapsed or refractory solid tumors to determine whether the four-drug combination can be given safely and the best dose of sorafenib when drug levels are adjusted based on blood tests (“PK-guided dosing”). - Part 2: Activity Study (Phase II)
After the safest dosing plan is identified, researchers study how well the treatment works, particularly in patients with FLC, HCC, desmoplastic small round cell tumor, and other rare solid tumors. The study aims not only to see whether tumors shrink, but also to understand how the treatment affects the immune system and tumor biology.
During the trial, patients will receive treatment in 21-day cycles:
- Cyclophosphamide: taken by mouth daily for 21 days.
- Sorafenib: taken by mouth daily, with dose adjustments based on blood levels.
- Bevacizumab: intravenous infusion every 3 weeks.
- Atezolizumab: intravenous infusion every 3 weeks.
To participate, patients must:
- Be under 30 years old.
- Have a relapsed or refractory solid tumor.
- Have disease that can be biopsied.
- Have adequate organ function and be healthy enough for treatment.
Trial contact information
The study is being conducted at the St. Jude Children’s Research Hospital, a leading pediatric cancer research center that never bills families for treatment. This allows parents to focus on their child’s care rather than the financial burden of illness.
- Email: referralinfo@stjude.org
- Phone: 888-226-4343
For more information about this trial, visit: https://clinicaltrials.gov/study/NCT05468359.
Please visit clinicaltrials.gov for a comprehensive list of active trials.
The Fibrolamellar Cancer Foundation does not provide medical advice. We provide website users with information to help them better understand their health conditions and current approaches towards diagnosis, treatment and supportive care. Always seek the advice of your physician or other qualified healthcare provider.