Liver CancerPhase 1NCT00507585
Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, Leucovorin, and Avastin
A Phase 1 study testing Fluorouracil, Avastin and Leucovorin in people with Liver Cancer and Advanced Solid Tumors, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
PRIMARY: To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Liver Cancer, Advanced Solid Tumors
- What is being tested?
- Fluorouracil, Avastin and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Jan 2010
- 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
- Patients with histologically confirmed metastatic advanced solid tumors involving the liver.
- Pediatric patients eligible at the discretion of the primary investigator.
- Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any work activities).
- Adequate renal function (Serum Creatinine </= 2.0 mg/dL) or a calculated creatinine clearance greater than 60 mL/min.
- Hepatic function as follows: In treatment arm 1: Total Bilirubin </= 3 mg/dL, AST </= 5 times upper normal reference value, or ALT </= 5 times upper normal reference value). In treatment arm 2: Total bilirubin >3 mg/dL. If bilirubin >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted.
- Adequate bone marrow function (ANC >/=1500 cells/uL; PLT >/= 100,000 cells/uL).
Show all 9Show fewer
- At least three weeks from previous immunotherapy, chemotherapy or radiotherapy before day of HAI infusion and recovery from any associated toxicities to less or equal to Grade 1.
- All females in childbearing age MUST have a negative serum HCG test unless prior hysterectomy or menopause (defined as age above 55 and six months without menstrual activity). Patients should not become pregnant or breast feed while on this study. Sexually active patients should use effective birth control.
- Ability to fully read, comprehend, and sign informed consent forms.
Who cannot join
- Clinical or radiographic evidence of ascites.
- Pregnant females.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function but not interfering with ADL)
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
Show all 14Show fewer
- Invasive procedures defined as follows; Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy, Anticipation of need for major surgical procedures during the course of the study, Core biopsy within 7 days prior to D1 of therapy.
- Patients receiving any other investigational agents.
- Patients with bleeding diathesis (clinical bleeding, prothrombin time =/> 1.5 X upper institutional normal value, INR =/> 1.5, activated partial thromboplastin time aPTT =/> 1.5 X upper institutional normal value), active gastric or duodenal ulcer.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
- Urine protein should be screened by dipstick or urine analysis. For proteinuria > 1+ or urine protein:creatinine ratio > 1.0, a 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with clinically significant cardiovascular disease: History of CVA within 6 months, myocardial infarction or unstable angina within 6 months, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris, clinically significant peripheral vascular disease
- Patients with history of bleeding CNS metastasis will be excluded from the trial.
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: A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients With Advanced Solid Tumors Metastatic to the Liver
PRIMARY:
- To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver.
SECONDARY:
- To document in a descriptive fashion the antitumor efficacy of this combination regimen.
- To evaluate the feasibility and accuracy of an alternate radiographic assessment tool and compare with available tumor markers and RECIST guidelines.
- To estimate in a descriptive fashion the development of extrahepatic tumor recurrences.
Read the detailed description
Oxaliplatin is designed to interfere with the growth of cancer cells (which slows their growth and spreading), eventually destroying them.
5-fluorouracil is designed to interfere with the growth of cells that reproduce rapidly.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to the 5-fluorouracil.
Bevacizumab is designed to interfere with blood flow to your tumors, which may cause tumors to be "starved" of the oxygen and nutrients they need to grow.
Before you can start 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 your complete medical history recorded and a physical exam, including measurement of your vital signs (blood pressure, temperature, breathing rate, and heart rate). You will have a neurological evaluation (a test to evaluate your strength and nerve functioning). You will have blood drawn (about 1 teaspoon or less) and urine collected for routine tests. Women who are able to have children must have a negative urine pregnancy test.
If you are found to be eligible to take part in this study, you will be hospitalized to receive the study drug combination. On the day of your admission to the hospital, you will have a catheter in your hepatic artery placed in your right groin. After your catheter has been placed, you will receive the study drugs. The catheter will be placed and removed during each cycle. A catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your physician will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.
You must lay in bed for the entire time that the catheter is in place. In some cases, the catheter will be removed immediately after your chemotherapy is complete. In some cases, the catheter may remain in overnight. Therefore, you must remain in bed until the catheter is removed.
During each cycle (on Days 1 and 2), you will receive 5-fluorouracil by vein continuously over 24 hours, leucovorin by vein over 1 hour, oxaliplatin by your hepatic artery over 2 hours, and bevacizumab by vein (only on Day 1) over about 1 1/2 hours. This study drug combination will be repeated about every 3 weeks, which is considered 1 cycle (about every 21 days).
To learn the highest tolerable dose of oxaliplatin when given in combination with the other study drugs, there will be a dose escalation process that will go as follows. The dose of oxaliplatin that you receive will depend on when you are enrolled in this study. The dose of the other 3 study drugs that you receive will be the same for each participant on this study. At first, 6 participants will be enrolled at the first dose level of oxaliplatin. If their disease does not get worse and no intolerable side effects occur, there will be another 6 patients enrolled at the next higher dose level. This dose escalation process will continue in this way until 8 dose levels have been reached without intolerable side effects occurring.
You will have blood drawn (about 2 teaspoons each) for blood counts and liver function tests before each dose of the study drug combination. This is so your doctor can check the safety of the drug combination. You will also have blood drawn (about 2 teaspoons each) before each cycle. The doctor will evaluate your disease and health before you receive the study drugs. Your tumors will be evaluated by the imaging scans (such as computed tomography [CT] and magnetic resonance imaging [MRI]) needed for your type of cancer. Imaging scans will be performed every 2 cycles.
You may continue to receive the study drug combination indefinitely as mentioned above unless your disease gets worse or you experience any intolerable side effects. If your disease gets worse or you experience any intolerable side effects, you will be removed from this study.
If your participation ends for any reason on this study (such as those mentioned above), you will have imaging scans (CT and MRI) to see if your tumors are growing or shrinking. You will have blood drawn (about 3 teaspoons) for routine tests. These end-of-study tests can be performed at your regular doctor's office, and the results will be sent to the study's research staff.
This is an investigational study. Oxaliplatin is authorized by the FDA for systemic use only. (Systemic therapies affect the body as a whole.) Giving oxaliplatin directly into the liver is investigational. 5-fluorouracil, leucovorin, and bevacizumab are FDA-approved for treatment of colorectal cancer. The use of these drugs in combination is authorized by the FDA for use in research only. Bevacizumab is not FDA-approved for all cancer types included in this study. Up to 163 patients will take part in this study. All patients will be enrolled at M. D. Anderson.
- Conditions
- Liver Cancer, Advanced Solid Tumors
- Being tested
- Fluorouracil, Avastin, Leucovorin, Oxaliplatin
- Keywords
- Liver Cancer, Liver metastases, Metastatic advanced solid tumors, Advanced solid tumors metastatic to the liver, Hepatic Arterial Infusion, Intra-arterial hepatic oxaliplatin, Fluorouracil, 5-FU, Adrucil, Efudex, 5-fluorouracil, Avastin, Leucovorin, Oxaliplatin, Bevacizumab
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluorouracilDrug
Also called 5-FU, Adrucil, Efudex, 5-fluorouracil
300 mg/m^2 IV over 10 Minutes, then 600 mg/m^2 IV over 22 Hours repeated every 3 weeks (1 Cycle).
AvastinDrug
Also called Bevacizumab
10 mg/m^2 IV Over 90 Minutes repeated every 3 weeks (1 Cycle).
LeucovorinDrug
200 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).
OxaliplatinDrug
60 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).
| Study group | Role | What they receive |
|---|---|---|
| Oxaliplatin + Fluorouracil + Leucovorin + Avastin | Experimental | Not described Receives: Drug: Fluorouracil; Drug: Avastin; Drug: Leucovorin; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver.
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2007 (estimated)
- Study startJun 2006
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Apostolia M. Tsimberidou, MD, PhD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00507585
- Sponsor's protocol ID
- 2006-0160
- Status last verified
- Jul 2012
- First submitted
- 24 Jul 2007
- Last updated
- 30 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients With Advanced Solid Tumors Metastatic to the Liver
- ClinicalTrials.gov ID
- NCT00507585
- Acronym / sponsor ID
- 2006-0160
- Conditions
- Liver Cancer, Advanced Solid Tumors
- Keywords
- Liver Cancer, Liver metastases, Metastatic advanced solid tumors, Advanced solid tumors metastatic to the liver, Hepatic Arterial Infusion, Intra-arterial hepatic oxaliplatin, Fluorouracil, 5-FU
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jun 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 26 Jul 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:
- To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver.
SECONDARY:
- To document in a descriptive fashion the antitumor efficacy of this combination regimen.
- To evaluate the feasibility and accuracy of an alternate radiographic assessment tool and compare with available tumor markers and RECIST guidelines.
- To estimate in a descriptive fashion the development of extrahepatic tumor recurrences.
Detailed description
Oxaliplatin is designed to interfere with the growth of cancer cells (which slows their growth and spreading), eventually destroying them.
5-fluorouracil is designed to interfere with the growth of cells that reproduce rapidly.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to the 5-fluorouracil.
Bevacizumab is designed to interfere with blood flow to your tumors, which may cause tumors to be "starved" of the oxygen and nutrients they need to grow.
Before you can start 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 your complete medical history recorded and a physical exam, including measurement of your vital signs (blood pressure, temperature, breathing rate, and heart rate). You will have a neurological evaluation (a test to evaluate your strength and nerve functioning). You will have blood drawn (about 1 teaspoon or less) and urine collected for routine tests. Women who are able to have children must have a negative urine pregnancy test.
If you are found to be eligible to take part in this study, you will be hospitalized to receive the study drug combination. On the day of your admission to the hospital, you will have a catheter in your hepatic artery placed in your right groin. After your catheter has been placed, you will receive the study drugs. The catheter will be placed and removed during each cycle. A catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your physician will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.
You must lay in bed for the entire time that the catheter is in place. In some cases, the catheter will be removed immediately after your chemotherapy is complete. In some cases, the catheter may remain in overnight. Therefore, you must remain in bed until the catheter is removed.
During each cycle (on Days 1 and 2), you will receive 5-fluorouracil by vein continuously over 24 hours, leucovorin by vein over 1 hour, oxaliplatin by your hepatic artery over 2 hours, and bevacizumab by vein (only on Day 1) over about 1 1/2 hours. This study drug combination will be repeated about every 3 weeks, which is considered 1 cycle (about every 21 days).
To learn the highest tolerable dose of oxaliplatin when given in combination with the other study drugs, there will be a dose escalation process that will go as follows. The dose of oxaliplatin that you receive will depend on when you are enrolled in this study. The dose of the other 3 study drugs that you receive will be the same for each participant on this study. At first, 6 participants will be enrolled at the first dose level of oxaliplatin. If their disease does not get worse and no intolerable side effects occur, there will be another 6 patients enrolled at the next higher dose level. This dose escalation process will continue in this way until 8 dose levels have been reached without intolerable side effects occurring.
You will have blood drawn (about 2 teaspoons each) for blood counts and liver function tests before each dose of the study drug combination. This is so your doctor can check the safety of the drug combination. You will also have blood drawn (about 2 teaspoons each) before each cycle. The doctor will evaluate your disease and health before you receive the study drugs. Your tumors will be evaluated by the imaging scans (such as computed tomography [CT] and magnetic resonance imaging [MRI]) needed for your type of cancer. Imaging scans will be performed every 2 cycles.
You may continue to receive the study drug combination indefinitely as mentioned above unless your disease gets worse or you experience any intolerable side effects. If your disease gets worse or you experience any intolerable side effects, you will be removed from this study.
If your participation ends for any reason on this study (such as those mentioned above), you will have imaging scans (CT and MRI) to see if your tumors are growing or shrinking. You will have blood drawn (about 3 teaspoons) for routine tests. These end-of-study tests can be performed at your regular doctor's office, and the results will be sent to the study's research staff.
This is an investigational study. Oxaliplatin is authorized by the FDA for systemic use only. (Systemic therapies affect the body as a whole.) Giving oxaliplatin directly into the liver is investigational. 5-fluorouracil, leucovorin, and bevacizumab are FDA-approved for treatment of colorectal cancer. The use of these drugs in combination is authorized by the FDA for use in research only. Bevacizumab is not FDA-approved for all cancer types included in this study. Up to 163 patients will take part in this study. All patients will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oxaliplatin + Fluorouracil + Leucovorin + Avastin | Experimental | Drug: Fluorouracil, Drug: Avastin, Drug: Leucovorin, Drug: Oxaliplatin |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with histologically confirmed metastatic advanced solid tumors involving the liver.
- Pediatric patients eligible at the discretion of the primary investigator.
- Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any work activities).
- Adequate renal function (Serum Creatinine </= 2.0 mg/dL) or a calculated creatinine clearance greater than 60 mL/min.
- Hepatic function as follows: In treatment arm 1: Total Bilirubin </= 3 mg/dL, AST </= 5 times upper normal reference value, or ALT </= 5 times upper normal reference value). In treatment arm 2: Total bilirubin >3 mg/dL. If bilirubin >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted.
Key exclusion criteria (14 listed)
- Clinical or radiographic evidence of ascites.
- Pregnant females.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function but not interfering with ADL)
- Serious or non-healing wound, ulcer or bone fracture.
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 |
|---|---|---|
| FluorouracilAlso: 5-FU, Adrucil, Efudex, 5-fluorouracil300 mg/m^2 IV over 10 Minutes, then 600 mg/m^2 IV over 22 Hours repeated every 3 weeks (1 Cycle). | Drug | Oxaliplatin + Fluorouracil + Leucovorin + Avastin |
| AvastinAlso: Bevacizumab10 mg/m^2 IV Over 90 Minutes repeated every 3 weeks (1 Cycle). | Drug | Oxaliplatin + Fluorouracil + Leucovorin + Avastin |
| Leucovorin200 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle). | Drug | Oxaliplatin + Fluorouracil + Leucovorin + Avastin |
| Oxaliplatin60 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle). | Drug | Oxaliplatin + Fluorouracil + Leucovorin + Avastin |
Primary outcome
To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver.
Time frame: 5 Years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2012.
- UT MD Anderson Cancer CenterLink provided by the sponsor.
Related trials for Liver Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
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.
Apostolia M. Tsimberidou, MD, PhD 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 Fluorouracil, Avastin and Leucovorin in people with Liver Cancer and Advanced Solid Tumors, 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 9 inclusion and 14 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: finished, as of the sponsor's last update on 30 Jul 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver. (time frame: 5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jul 2012.