Proton Therapy and Bevacizumab for Primary Liver Tumors

NCT00426829 | Terminated Phase 1

• 1 other identifier: 2005-0881
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

1. 1.To evaluate the safety of the treatment of patients with technically or medically inoperable hepatocellular carcinoma and cholangiocarcinoma with proton therapy and concurrent bevacizumab biotherapy.
2. 2.To identify the maximum tolerated dose (MTD) using this combination.
3. 3.To evaluate local control rate within the radiation field, hepatic control rate outside the treatment field, time to radiographic progression and 2 year survival rate.
4. 4.To analyze dose-volume characteristics that influence the development of radiation induced liver disease (RILD) and GI bleeds that may occur.
5. 5.To assess quality of life during and after chemoradiation therapy.

Conditions

Liver Cancer; Hepatocellular Carcinoma; Cholangiocarcinoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

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

Study Arms (1)

Proton Therapy + Bevacizumab

EXPERIMENTAL

Proton Therapy + Bevacizumab

Drug: Bevacizumab; Radiation: Proton Radiation Therapy

Interventions

Bevacizumab DRUG

10 mg/kg by vein every 14 days +/- 2 days, starting on day 1.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Proton Therapy + Bevacizumab

Proton Radiation Therapy RADIATION

3 Gy dose/fraction x 20 fractions.

Also known as: PT, RT, Proton RT

Proton Therapy + Bevacizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \</= 1.5 mg/dl.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 3 times the upper limit of normal. Serum bilirubin \</= 5mg/dL prior to the start of therapy.
• A signed study-specific consent form, which is attached to this protocol.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

U.T. M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Zhang X, Li G, Li X, Liang Z, Lan X, Mou T, Xu Z, Fu J, Wu M, Li G, Wang Y. Effect of single-incision plus one port laparoscopic surgery assisted with enhanced recovery after surgery on colorectal cancer: study protocol for a single-arm trial. Transl Cancer Res. 2021 Dec;10(12):5443-5453. doi: 10.21037/tcr-21-1361.

  PMID: 35116390 DERIVED

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular; Cholangiocarcinoma

Interventions

Bevacizumab; Protons

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena

Study Officials

• Sunil Krishnan, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 23, 2007
• First Posted: January 25, 2007
• Study Start: May 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 1, 2012

Record last verified: 2012-07

Locations

US (1)