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Phase I Study of Proton Radiotherapy and Bevacizumab for Primary Liver Tumors

Phase 1
Not Enrolling
Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma

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Trial Information

Phase I Study of Proton Radiotherapy and Bevacizumab for Primary Liver Tumors

Proton beams are designed to deliver a high dose of radiation to the abnormal tissues while
sparing surrounding normal tissues. Bevacizumab is a biotherapy that is designed to prevent
or slow down the growth of cancer cells by blocking the growth of blood vessels.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. You will have a
complete physical exam. Blood (about 2 tablespoons) and urine will be collected for routine
tests. You will have chest x-rays and a computed tomography (CT) scan of your abdomen
(stomach area) and pelvis. Women who are able to have a children must have a negative urine
pregnancy test.

You will then have a radiation treatment planning session called a simulation. You will get
a CT scan of your abdomen, and marks will be placed on your skin to help guide the radiation
treatments when you return for the actual treatments. At around the same time, you will
receive your first dose of bevacizumab through a needle in your vein. The infusion will at
first last 90 minutes. If there are no allergic reactions, fevers, or chills, the infusion
will be shortened to 60 minutes and then 30 minutes for later infusions. Your second dose of
bevacizumab will be given with the start of radiation therapy treatments. Your final dose of
bevacizumab will be given 2 weeks later. You will receive radiation therapy once a day, for
5 days in a row (Monday-Friday) for 4 weeks (total of 20 treatments).

During this study, you will have physical exams weekly during treatment, 1 month after the
last proton beam therapy visit and then every 3 months thereafter. Every week, while
receiving proton beam therapy, blood (about 2 teaspoons) will be drawn to check for any
side effects. You will be asked about any side effects you may be experiencing.

You may remain on study for as long as you are benefitting. You will be taken off study if
the disease gets worse or intolerable side effects occur.

After participation in this study is over, you will have follow-up evaluation every 3 months
for 2 years. During these visits, you will have a physical exam. You will have CT scans.
Blood (about 2 teaspoons) will be drawn for routine tests.

This is an investigational study. Bevacizumab is FDA approved and commercially available
for the treatment of metastatic colon cancer. The use of bevacizumab with proton beam
therapy is investigational. Up to 30 patients will take part in this study. All will be
enrolled at M. D. Anderson.

Inclusion Criteria:

- Cytologic or histologic proof of primary liver cancer (hepatocellular carcinoma or
cholangiocarcinoma). Patients with non-metastatic, unresectable disease are eligible.
Patients with positive margins after surgical resection are eligible. Metastasis is
defined as unequivocal evidence of extrahepatic disease based on CT imaging,
excluding nodal disease.

- Tumors must not be greater than 10cm (small satellite lesions around a larger lesion
are allowed), all of which can be encompassed in a radiation treatment field (as
assessed by the radiation oncologist).

- Prior chemotherapy, transarterial chemoembolization and radiofrequency ablation are
permitted. A minimum of four weeks must have elapsed between prior treatment and
planned protocol therapy.

- Prior liver resection is permitted as long as the interval between surgery and
enrollment is at least 4 weeks.

- Karnofsky performance status >/= 70 are eligible.

- There is no age restriction.

- Absolute granulocyte count >/= 1,500 cells/mm3, hemoglobin >/= 8 gm/dL and platelet
count >/= 80,000 cells/mm3.

- Serum creatinine
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) upper limit of normal. Serum bilirubin
- A signed study-specific consent form, which is attached to this protocol.

Exclusion Criteria:

- Child-Pugh class C cirrhosis.

- Gross ascites seen on CT that precludes accurate targeting of the tumor with
radiation therapy

- Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC)
ratio > 1.0 at screening OR Urine dipstick for proteinuria > 2+ (patients discovered
to have > 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour
urine collection and must demonstrate < 1g of protein in 24 hours to be eligible).

- Patients currently receiving anticoagulation treatment with coumadin, low molecular
weight heparin or IV heparin. Evidence of bleeding diathesis or coagulopathy.
Anticoagulation for line maintenance is permitted.

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, or anticipation of need for major surgical procedure during the
course of the study; fine needle aspirations or core biopsies within 7 days prior to
Day 0.

- Serious, nonhealing wound, ulcer, or bone fracture.

- Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood
pressure of >150/100 mmHg on medication], history of myocardial infarction within 6
months, unstable angina), New York Heart Association (NYHA) Class II or greater
congestive heart failure, unstable symptomatic arrhythmia requiring medication
(subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal
supraventricular tachycardia are eligible), or Class II or greater peripheral
vascular disease.

- History of aneurysms, strokes, transient ischemic attacks, and arteriovenous
malformations within 6 months.

- Prior unanticipated severe reaction to bevacizumab.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0

- Patients who have had an organ allograft.

- Pregnant women are excluded from this study; women of childbearing potential must
agree to practice adequate contraception (oral, injectable, or implantable hormonal
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with
spermicide; or vasectomized partner) and to refrain from breast feeding, as specified
in the informed consent. Women of child-bearing potential are defined as those women
who have not had surgical sterilization or been menopausal for 12 consecutive months.

- Male patients must agree not to father a child and must agree to use a condom.

- Prior radiation therapy to an upper abdominal or lower thoracic field that could
overlap with the proposed treatment field.

- Serious concomitant medical or psychiatric disorders that place the patient at high
risk for non-compliance with or morbidity due to protocol therapy.

- Patients with a history of hypertension must be well-controlled ( stable regimen of antihypertensive therapy)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity (during and within 1 month after completion of radiotherapy)

Outcome Time Frame:

1 month +/- 1 week upon completion of concurrent chemoradiation

Safety Issue:


Principal Investigator

Sunil Krishnan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

May 2007

Completion Date:

November 2009

Related Keywords:

  • Liver Cancer
  • Hepatocellular Carcinoma
  • Cholangiocarcinoma
  • Liver Cancer
  • Biliary Tract
  • Hepatocellular Carcinoma
  • Cholangiocarcinoma
  • Bevacizumab
  • Proton Therapy
  • Radiation Therapy
  • PT
  • RT
  • Proton RT
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Carcinoma
  • Liver Neoplasms
  • Cholangiocarcinoma
  • Carcinoma, Hepatocellular



U.T. M.D. Anderson Cancer Center Houston, Texas  77030