Liver CancerPhase 1NCT00426829
Proton Therapy and Bevacizumab for Primary Liver Tumors
A Phase 1 study testing Bevacizumab and Proton Radiation Therapy in people with Liver Cancer and Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objectives: 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. To identify the maximum tolerated dose (MTD) using this combination. Secondary Objectives: 1. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
- What is being tested?
- Bevacizumab and Proton Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Nov 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 (</= 140/90 mmHg on a stable regimen of antihypertensive therapy)
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T. M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I Study of Proton Radiotherapy and Bevacizumab for Primary Liver Tumors
Primary Objectives:
- 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.
- To identify the maximum tolerated dose (MTD) using this combination.
Secondary Objectives:
- 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.
- To analyze dose-volume characteristics that influence the development of radiation induced liver disease (RILD) and GI bleeds that may occur.
- To assess quality of life during and after chemoradiation therapy.
Read the detailed description
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.
- Conditions
- Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
- Being tested
- Bevacizumab, Proton Radiation Therapy
- Keywords
- Liver Cancer, Biliary Tract, Hepatocellular Carcinoma, Cholangiocarcinoma, Bevacizumab, Proton Therapy, Radiation Therapy, PT, RT, Proton RT, Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
10 mg/kg by vein every 14 days +/- 2 days, starting on day 1.
Proton Radiation TherapyRadiation
Also called PT, RT, Proton RT
3 Gy dose/fraction x 20 fractions.
| Study group | Role | What they receive |
|---|---|---|
| Proton Therapy + Bevacizumab | Experimental | Proton Therapy + Bevacizumab Receives: Drug: Bevacizumab; Radiation: Proton Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity (during and within 1 month after completion of radiotherapy)
Measured: 1 month +/- 1 week upon completion of concurrent chemoradiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2007 (estimated)
- Study startMay 2007
- Primary completionNov 2009
- Study completionNov 2009
Why it stopped: Low Accural
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Sunil Krishnan, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00426829
- Sponsor's protocol ID
- 2005-0881
- Status last verified
- Jul 2012
- First submitted
- 23 Jan 2007
- Last updated
- 1 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 35116390
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Proton Radiotherapy and Bevacizumab for Primary Liver Tumors
- ClinicalTrials.gov ID
- NCT00426829
- Acronym / sponsor ID
- 2005-0881
- Conditions
- Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
- Keywords
- Liver Cancer, Biliary Tract, Hepatocellular Carcinoma, Cholangiocarcinoma, Bevacizumab, Proton Therapy, Radiation Therapy, PT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accural
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- May 2007
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 25 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
- 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.
- To identify the maximum tolerated dose (MTD) using this combination.
Secondary Objectives:
- 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.
- To analyze dose-volume characteristics that influence the development of radiation induced liver disease (RILD) and GI bleeds that may occur.
- To assess quality of life during and after chemoradiation therapy.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Proton Therapy + Bevacizumab | Experimental | Drug: Bevacizumab, Radiation: Proton Radiation TherapyProton Therapy + Bevacizumab |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF10 mg/kg by vein every 14 days +/- 2 days, starting on day 1. | Drug | Proton Therapy + Bevacizumab |
| Proton Radiation TherapyAlso: PT, RT, Proton RT3 Gy dose/fraction x 20 fractions. | Radiation | Proton Therapy + Bevacizumab |
Primary outcome
Toxicity (during and within 1 month after completion of radiotherapy)
Time frame: 1 month +/- 1 week upon completion of concurrent chemoradiation
Results and safety
The study was stopped early (reason given: Low Accural). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
- Derived from this study: PubMed 35116390Zhang 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.
- UT MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sunil Krishnan, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab and Proton Radiation Therapy in people with Liver Cancer and Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low Accural). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity (during and within 1 month after completion of radiotherapy) (time frame: 1 month +/- 1 week upon completion of concurrent chemoradiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00426829, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2012.