Advanced CancersPhase 1NCT00941499
Hepatic Arterial Infusion Oxaliplatin + 5FU, Leucovorin, and Bevacizumab +/- Cetuximab
A Phase 1 study testing HAI Oxaliplatin, 5-FU and Bevacizumab in people with Advanced Cancers, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the best combination of oxaliplatin, bevacizumab, 5-fluorouracil, leucovorin, and cetuximab that can be given to patients with advanced cancer that has spread to the liver. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Cancers
- What is being tested?
- HAI Oxaliplatin, 5-FU and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to May 2014
- 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 must have histologically confirmed cancer with metastatic liver metastases.
- Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months, unless the drugs in the protocol regimen are part of the standard of care.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (Capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
- Adequate renal function (Serum Creatinine </= 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
- Patients will be stratified by liver function tests: Normal liver function: Total Bilirubin </= 3 mg/dL, Alanine aminotransferase (ALT) </= 5 times upper normal reference value. Abnormal liver function: Total bilirubin >3 mg/dL and/or elevated ALT > 5 x upper limit of normal (ULN). If bilirubin is >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted. Both of the above groups will be eligible.
- Adequate bone marrow function (Absolute Neutrophil Count (ANC) >/=1500 cells/uL; Platelets (PLT) >/= 100,000 cells/uL).
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- At least three weeks from previous cytotoxic chemotherapy before day 1 of hepatic arterial infusion (HAI) infusion. After targeted or biologic therapy, there should be 5 half-lives or three weeks, whichever is shorter.
- All females in childbearing age MUST have a negative urine human chorionic gonadotropin (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 sign informed consent form. Pediatric: age 7-18 would sign assent, (<7 would not assent), parent or guardian would sign consent.
- Patients with colorectal cancer must agree to K-RAS mutational status screening, if not available. If tissue is not available, patients can enter on trial, but not on the cetuximab arms.
Who cannot join
- Pregnant females.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients already in uncompensated liver failure (i.e. Child Pugh Liver Classification C).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Bevacizumab With/Without Cetuximab by K-RAS Mutational Status and Liver Function for Advanced Cancers Metastatic to the Liver
The goal of this clinical research study is to find the best combination of oxaliplatin, bevacizumab, 5-fluorouracil, leucovorin, and cetuximab that can be given to patients with advanced cancer that has spread to the liver. Different combinations of these drugs will be used, and the safety of all drug combinations will also be studied.
Read the detailed description
The Study Drugs:
Oxaliplatin is designed to keep new cancer cells from growing.
5-fluorouracil is designed to block the way cancer cells grow and divide, which may slow or stop their growth and keep them from spreading throughout the body. This may cause the cancer cells to die.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to 5-fluorouracil. BECAUSE OF A PHARMACY SHORTAGE OF IV LEUCOVORIN, PATIENTS WILL CONTINUE TREATMENT WITHOUT LEUCOVORIN UNTIL IT BECOMES AVAILABLE.
Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the epidermal growth factor receptor (EGFR).
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study "arm" (group) based on the results of your screening tests. All patients will receive oxaliplatin and bevacizumab. If your doctor thinks it is in your best interest, you will also receive cetuximab. However, recent studies have found that cetuximab, when given alone or in combination with other chemotherapy drugs, was not effective when given to patients with colorectal cancer that had a K-RAS mutation. If you have colorectal cancer and you are tested for and do not have the K-RAS gene, you will also receive cetuximab. Patients with normal liver function will also receive 5-FU.
- If you are in Arm A, you will receive oxaliplatin, 5-FU, and bevacizumab.
- If you are in Arm B, you will receive oxaliplatin, 5-FU, leucovorin, bevacizumab, and cetuximab.
- If you are in Arm C, you will receive oxaliplatin and bevacizumab.
- If you are in Arm D, you will receive oxaliplatin, bevacizumab, and cetuximab.
Arm A:
All participants will receive the same dose levels of oxaliplatin and bevacizumab.
You will be assigned to a dose level of 5-FU based on when you joined this study. Up to 4 dose levels of 5-FU will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm B:
All participants will receive the same dose levels of oxaliplatin, bevacizumab, and leucovorin.
You will be assigned to a combination dose level of 5-FU and cetuximab based on when you joined this study. Up to 4 combination dose levels of 5-FU and cetuximab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm C:
All participants will receive the same dose levels of oxaliplatin.
You will be assigned to a dose level of bevacizumab based on when you joined this study. Up to 4 dose levels of bevacizumab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm D:
All participants will receive the same dose levels of oxaliplatin.
You will be assigned to a combination dose level of bevacizumab and cetuximab based on when you joined this study. Up to 4 combination dose levels of bevacizumab and cetuximab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
In each group, after the highest tolerable dose of the study drug combination is found, up to 12 additional patients will receive that dose level.
Additionally, for Arm A and Arm B, after the highest tolerable dose of the study drug combination is found, up to 20 additional participants with colorectal cancer will be added to Arm A and Arm B.
Catheter Placement for Study Drug Administration:
You will be hospitalized to receive the study drug combination. On the day of your admission to the hospital, you will have a catheter (a sterile flexible tube that will be placed in the hepatic artery [a blood vessel in the liver] while you are under local anesthesia) through which you will receive the study drugs. The catheter will be placed and removed during each cycle. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
You must lay in bed for the entire time that the catheter is in place. In some cases, the catheter will be removed right 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.
Study Drug Administration:
Arm A:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours. You will then receive 5-FU over 24 hours through the hepatic arterial catheter. You will then receive bevacizumab by vein over 1 1/2 hours.
Arm B:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and 5-FU and leucovorin by vein over 24 hours on Days 1 and 2 of each cycle (a total of 48 hours). You will then receive bevacizumab by vein over about 1 1/2 hours, followed by cetuximab by vein over 1-2 hours.
Arm C:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and bevacizumab by vein over about 1 1/2 hours.
Arm D:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and you will receive bevacizumab by vein over about 1 1/2 hours. You will also receive cetuximab by vein over about 1-2 hours on Day 1 of each cycle.
Study Visits:
At each study visit, you will be asked about any other drugs you may be receiving and about any side effects you may be having.
On Day 1 of Cycle 1:
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be used to test your blood's ability to clot.
- If your study doctor thinks it is needed, you will have an ECG.
- Women who are able to become pregnant will have a urine pregnancy test.
On Day 2 of Cycle 1:
-You will have a physical exam, including measurement of your weight and vital signs.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- If your study doctor thinks it is needed, you will have an ECG.
- Women who are able to become pregnant will have a urine pregnancy test.
On Day 2 of Cycles 2 and beyond:
-You will have a physical exam, including measurement of your weight and vital signs.
At the end of each cycle, blood (about 1 teaspoon) will be drawn to test your blood's ability to clot.
At the end of Cycle 2 and then every 2-3 cycles after that, you will have scans to check the status of the disease. This may include a chest x-ray, CT scan, MRI scan, a PET scan and/or a PET/CT scan. If the study doctor thinks it is more appropriate for you, other types of scans may need to be performed. The study doctor will discuss these scans with you, and you may be asked to sign a separate consent form.
Length of Study:
You may continue to receive the study drug combination for as long as you are benefitting. You will be taken off study if the disease gets worse or if you experience any intolerable side effects.
Follow-Up:
About 6 weeks after your last dose of study drugs, the following tests and procedures will be performed:
- Blood (about 3 teaspoons) will be drawn for routine tests.
- You will have a physical exam, including measurement of your weight and vital signs.
This is an investigational study. All of the study drugs are FDA-approved and commercially available for use in other types of cancer:
- 5-FU - for cancers of the breast, pancreas, colon/rectum, stomach, and a type of skin cancer (superficial basal cell carcinoma).
- Oxaliplatin and leucovorin - for colorectal cancer.
- Bevacizumab - for colorectal and lung cancers.
- Cetuximab - for colorectal and head/neck cancers.
It is investigational to give the study drugs together for advanced cancer.
Up to 198 participants will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Advanced Cancers
- Being tested
- HAI Oxaliplatin, 5-FU, Bevacizumab, Cetuximab, Leucovorin
- Keywords
- Advanced Cancers, Liver, Oxaliplatin, Eloxatin, Bevacizumab, Avastin, Anit-VEGF monoclonal antibody, rhuMAb-VEGF, 5-fluorouracil, 5-FU, Adrucil, Efudex, Leucovorin, Citrovorum, Wellcovorin, Cetuximab, C225, Erbitux, IMC-C225
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAI OxaliplatinDrug
Also called Eloxatin
140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle
5-FUDrug
Also called 5-Fluorouracil, Adrucil, Efudex
900-1750 mg/m^2 HAI infusion over 24 hours on Days 1 - 2 of each 21 day cycle.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
10 mg/Kg by vein on Day 1 of 21 day cycle.
CetuximabDrug
Also called C225, Erbitux, IMC-C225
Loading dose of 250-500mg/m^2 and Maintenance dose of 125-250 mg/m^2 by vein on Day 1 of 21 day cycle.
LeucovorinDrug
Also called Citrovorum, Wellcovorin
200 mg/m^2 by vein on Days 1 and 2 of each 21 day cycle.
5-FUDrug
Also called 5-Fluorouracil, Adrucil, Efudex
300-400 mg/m^2 bolus + 600-1000 mg/m^2 infusion over 22 hours on Days 1-2 of each cycle.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
7.5 - 15 mg/Kg by vein on Day 1 of 21 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | HAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab Receives: Drug: HAI Oxaliplatin; Drug: 5-FU; Drug: Bevacizumab |
| Group 2 | Experimental | HAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab Receives: Drug: HAI Oxaliplatin; Drug: Bevacizumab; Drug: Leucovorin; Drug: 5-FU |
| Group 3 | Experimental | HAI oxaliplatin in combination with IV bevacizumab. Receives: Drug: HAI Oxaliplatin; Drug: Bevacizumab |
| Group 4 | Experimental | HAI oxaliplatin in combination with IV bevacizumab and cetuximab. Receives: Drug: HAI Oxaliplatin; Drug: Cetuximab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin
If more than 33% of patients enrolled in any particular dose level develop DLT, the treatment will continue at the dose level immediately below. If not more than 33% of the patients in the cohort develop DLT, this cohort will be considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v3.0, any Grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI CTC), despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in the NCI CTC. The MTD defined by DLTs that occur in the first cycle.
Measured: 21 days
Anti-Tumor Efficacy
Response Evaluation Criteria in Solid Tumors (RECIST) guidelines used to assess the efficacy of this regimen. A 20% increase in the sum of the greatest longitudinal diameters considered stable disease in the absence of clinical symptoms. An exploratory analysis of radiographic tool measuring the diameter of tumor lesions and comparing their tissue density in comparison with liver function studies and serum biochemical markers performed among study participants.
Measured: After 2, 21 day cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancersStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 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, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00941499
- Sponsor's protocol ID
- 2009-0023
- Other IDs
- NCI-2011-00538
- Status last verified
- Nov 2015
- First submitted
- 15 Jul 2009
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Bevacizumab With/Without Cetuximab by K-RAS Mutational Status and Liver Function for Advanced Cancers Metastatic to the Liver
- ClinicalTrials.gov ID
- NCT00941499
- Acronym / sponsor ID
- 2009-0023
- Conditions
- Advanced Cancers
- Keywords
- Advanced Cancers, Liver, Oxaliplatin, Eloxatin, Bevacizumab, Avastin, Anit-VEGF monoclonal antibody, rhuMAb-VEGF
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 17 Jul 2009 (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.
The goal of this clinical research study is to find the best combination of oxaliplatin, bevacizumab, 5-fluorouracil, leucovorin, and cetuximab that can be given to patients with advanced cancer that has spread to the liver. Different combinations of these drugs will be used, and the safety of all drug combinations will also be studied.
Detailed description
The Study Drugs:
Oxaliplatin is designed to keep new cancer cells from growing.
5-fluorouracil is designed to block the way cancer cells grow and divide, which may slow or stop their growth and keep them from spreading throughout the body. This may cause the cancer cells to die.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to 5-fluorouracil. BECAUSE OF A PHARMACY SHORTAGE OF IV LEUCOVORIN, PATIENTS WILL CONTINUE TREATMENT WITHOUT LEUCOVORIN UNTIL IT BECOMES AVAILABLE.
Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the epidermal growth factor receptor (EGFR).
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study "arm" (group) based on the results of your screening tests. All patients will receive oxaliplatin and bevacizumab. If your doctor thinks it is in your best interest, you will also receive cetuximab. However, recent studies have found that cetuximab, when given alone or in combination with other chemotherapy drugs, was not effective when given to patients with colorectal cancer that had a K-RAS mutation. If you have colorectal cancer and you are tested for and do not have the K-RAS gene, you will also receive cetuximab. Patients with normal liver function will also receive 5-FU.
- If you are in Arm A, you will receive oxaliplatin, 5-FU, and bevacizumab.
- If you are in Arm B, you will receive oxaliplatin, 5-FU, leucovorin, bevacizumab, and cetuximab.
- If you are in Arm C, you will receive oxaliplatin and bevacizumab.
- If you are in Arm D, you will receive oxaliplatin, bevacizumab, and cetuximab.
Arm A:
All participants will receive the same dose levels of oxaliplatin and bevacizumab.
You will be assigned to a dose level of 5-FU based on when you joined this study. Up to 4 dose levels of 5-FU will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm B:
All participants will receive the same dose levels of oxaliplatin, bevacizumab, and leucovorin.
You will be assigned to a combination dose level of 5-FU and cetuximab based on when you joined this study. Up to 4 combination dose levels of 5-FU and cetuximab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm C:
All participants will receive the same dose levels of oxaliplatin.
You will be assigned to a dose level of bevacizumab based on when you joined this study. Up to 4 dose levels of bevacizumab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
Arm D:
All participants will receive the same dose levels of oxaliplatin.
You will be assigned to a combination dose level of bevacizumab and cetuximab based on when you joined this study. Up to 4 combination dose levels of bevacizumab and cetuximab will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
In each group, after the highest tolerable dose of the study drug combination is found, up to 12 additional patients will receive that dose level.
Additionally, for Arm A and Arm B, after the highest tolerable dose of the study drug combination is found, up to 20 additional participants with colorectal cancer will be added to Arm A and Arm B.
Catheter Placement for Study Drug Administration:
You will be hospitalized to receive the study drug combination. On the day of your admission to the hospital, you will have a catheter (a sterile flexible tube that will be placed in the hepatic artery [a blood vessel in the liver] while you are under local anesthesia) through which you will receive the study drugs. The catheter will be placed and removed during each cycle. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
You must lay in bed for the entire time that the catheter is in place. In some cases, the catheter will be removed right 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.
Study Drug Administration:
Arm A:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours. You will then receive 5-FU over 24 hours through the hepatic arterial catheter. You will then receive bevacizumab by vein over 1 1/2 hours.
Arm B:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and 5-FU and leucovorin by vein over 24 hours on Days 1 and 2 of each cycle (a total of 48 hours). You will then receive bevacizumab by vein over about 1 1/2 hours, followed by cetuximab by vein over 1-2 hours.
Arm C:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and bevacizumab by vein over about 1 1/2 hours.
Arm D:
On day 1 of each 21 day cycle you will receive oxaliplatin through the hepatic arterial catheter over 2 hours and you will receive bevacizumab by vein over about 1 1/2 hours. You will also receive cetuximab by vein over about 1-2 hours on Day 1 of each cycle.
Study Visits:
At each study visit, you will be asked about any other drugs you may be receiving and about any side effects you may be having.
On Day 1 of Cycle 1:
- Your medical history will be recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- Blood (about 1 teaspoon) will be used to test your blood's ability to clot.
- If your study doctor thinks it is needed, you will have an ECG.
- Women who are able to become pregnant will have a urine pregnancy test.
On Day 2 of Cycle 1:
-You will have a physical exam, including measurement of your weight and vital signs.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam, including measurement of your weight and vital signs.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- If your study doctor thinks it is needed, you will have an ECG.
- Women who are able to become pregnant will have a urine pregnancy test.
On Day 2 of Cycles 2 and beyond:
-You will have a physical exam, including measurement of your weight and vital signs.
At the end of each cycle, blood (about 1 teaspoon) will be drawn to test your blood's ability to clot.
At the end of Cycle 2 and then every 2-3 cycles after that, you will have scans to check the status of the disease. This may include a chest x-ray, CT scan, MRI scan, a PET scan and/or a PET/CT scan. If the study doctor thinks it is more appropriate for you, other types of scans may need to be performed. The study doctor will discuss these scans with you, and you may be asked to sign a separate consent form.
Length of Study:
You may continue to receive the study drug combination for as long as you are benefitting. You will be taken off study if the disease gets worse or if you experience any intolerable side effects.
Follow-Up:
About 6 weeks after your last dose of study drugs, the following tests and procedures will be performed:
- Blood (about 3 teaspoons) will be drawn for routine tests.
- You will have a physical exam, including measurement of your weight and vital signs.
This is an investigational study. All of the study drugs are FDA-approved and commercially available for use in other types of cancer:
- 5-FU - for cancers of the breast, pancreas, colon/rectum, stomach, and a type of skin cancer (superficial basal cell carcinoma).
- Oxaliplatin and leucovorin - for colorectal cancer.
- Bevacizumab - for colorectal and lung cancers.
- Cetuximab - for colorectal and head/neck cancers.
It is investigational to give the study drugs together for advanced cancer.
Up to 198 participants will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: HAI Oxaliplatin, Drug: 5-FU, Drug: BevacizumabHAI oxaliplatin in combination with HAI 5-fluorouracil and IV bevacizumab |
| Group 2 | Experimental | Drug: HAI Oxaliplatin, Drug: Bevacizumab, Drug: Leucovorin, Drug: 5-FUHAI oxaliplatin in combination with IV 5-fluorouracil, leucovorin, bevacizumab, and cetuximab |
| Group 3 | Experimental | Drug: HAI Oxaliplatin, Drug: BevacizumabHAI oxaliplatin in combination with IV bevacizumab. |
| Group 4 | Experimental | Drug: HAI Oxaliplatin, Drug: Cetuximab, Drug: BevacizumabHAI oxaliplatin in combination with IV bevacizumab and cetuximab. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have histologically confirmed cancer with metastatic liver metastases.
- Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months, unless the drugs in the protocol regimen are part of the standard of care.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (Capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
- Adequate renal function (Serum Creatinine </= 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
- Patients will be stratified by liver function tests: Normal liver function: Total Bilirubin </= 3 mg/dL, Alanine aminotransferase (ALT) </= 5 times upper normal reference value. Abnormal liver function: Total bilirubin >3 mg/dL and/or elevated ALT > 5 x upper limit of normal (ULN). If bilirubin is >/= 5 mg/dL, fluorouracil (5FU) dose will be omitted. Both of the above groups will be eligible.
Key exclusion criteria (7 listed)
- Pregnant females.
- Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
- Serious or non-healing wound, ulcer or bone fracture.
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg).
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 |
|---|---|---|
| HAI OxaliplatinAlso: Eloxatin140 mg/m^2 by HAI (hepatic arterial infusion)over 2 hours on Day 1 of each 21 day cycle | Drug | Group 1, Group 2, Group 3, Group 4 |
| 5-FUAlso: 5-Fluorouracil, Adrucil, Efudex900-1750 mg/m^2 HAI infusion over 24 hours on Days 1 - 2 of each 21 day cycle. | Drug | Group 1 |
| BevacizumabAlso: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF10 mg/Kg by vein on Day 1 of 21 day cycle. | Drug | Group 1, Group 2, Group 3 |
| CetuximabAlso: C225, Erbitux, IMC-C225Loading dose of 250-500mg/m^2 and Maintenance dose of 125-250 mg/m^2 by vein on Day 1 of 21 day cycle. | Drug | Group 4 |
| LeucovorinAlso: Citrovorum, Wellcovorin200 mg/m^2 by vein on Days 1 and 2 of each 21 day cycle. | Drug | Group 2 |
| 5-FUAlso: 5-Fluorouracil, Adrucil, Efudex300-400 mg/m^2 bolus + 600-1000 mg/m^2 infusion over 22 hours on Days 1-2 of each cycle. | Drug | Group 2 |
| BevacizumabAlso: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF7.5 - 15 mg/Kg by vein on Day 1 of 21 day cycle. | Drug | Group 4 |
Primary outcome
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin
Time frame: 21 days
If more than 33% of patients enrolled in any particular dose level develop DLT, the treatment will continue at the dose level immediately below. If not more than 33% of the patients in the cohort develop DLT, this cohort will be considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v3.0, any Grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI CTC), despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in the NCI CTC. The MTD defined by DLTs that occur in the first cycle.
Anti-Tumor Efficacy
Time frame: After 2, 21 day cycles
Response Evaluation Criteria in Solid Tumors (RECIST) guidelines used to assess the efficacy of this regimen. A 20% increase in the sum of the greatest longitudinal diameters considered stable disease in the absence of clinical symptoms. An exploratory analysis of radiographic tool measuring the diameter of tumor lesions and comparing their tissue density in comparison with liver function studies and serum biochemical markers performed among study participants.
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 18 Nov 2015.
- University of Texas MD Anderson Cancer Center WebsiteLink 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.
Apostolia M. Tsimberidou, MD, PHD study chair
UT MD 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 HAI Oxaliplatin, 5-FU and Bevacizumab in people with Advanced Cancers, 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 7 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 18 Nov 2015. 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?
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of Intra-Arterial Hepatic Oxaliplatin (time frame: 21 days). The study lists 2 primary outcomes in all. 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 18 Nov 2015.