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
N/A
N/A
Both
Liver Cancer, Advanced Solid Tumors
Trial Information
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
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.
Inclusion Criteria:
1. Patients with histologically confirmed metastatic advanced solid tumors involving the
liver.
2. Pediatric patients eligible at the discretion of the primary investigator.
3. Performance status ECOG 0-2 (Capable of all self care but unable to to carry out any
work activities).
4. Adequate renal function (Serum Creatinine clearance greater than 60 mL/min.
5. Hepatic function as follows: In treatment arm 1: Total Bilirubin 5 times upper normal reference value, or ALT value). In treatment arm 2: Total bilirubin >3 mg/dL. If bilirubin >/= 5 mg/dL,
fluorouracil (5FU) dose will be omitted.
6. Adequate bone marrow function (ANC >/=1500 cells/uL; PLT >/= 100,000 cells/uL).
7. 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.
8. 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.
9. Ability to fully read, comprehend, and sign informed consent forms.
Exclusion Criteria:
1. Clinical or radiographic evidence of ascites.
2. Pregnant females.
3. Inability to complete informed consent process and adhere to protocol treatment plan
and follow-up requirements.
4. Grade 2 Peripheral Neuropathy (CTC V3.0: Sensory alteration interfering with function
but not interfering with ADL)
5. Serious or non-healing wound, ulcer or bone fracture.
6. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 28 days.
7. 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.
8. Patients receiving any other investigational agents.
9. 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.
10. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg,
Diastolic Blood Pressure > 90 mmHg).
11. 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.
12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit compliance with
study requirements.
13. 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
14. Patients with history of bleeding CNS metastasis will be excluded from the trial.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Outcome Time Frame:
5 Years
Safety Issue:
Yes
Principal Investigator
Apostolia M. Tsimberidou, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2006-0160
NCT ID:
NCT00507585
Start Date:
June 2006
Completion Date:
January 2010
Related Keywords:
- Liver Cancer
- Advanced Solid Tumors
- 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
- Liver Neoplasms
- Neoplasms
Name | Location |
|---|---|
| U.T.M.D. Anderson Cancer Center | Houston, Texas 77030 |
