HAI Abraxane With Gemcitabine and Bevacizumab

NCT ID: NCT01057264

Last Updated: 2015-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2014-05-31

Brief Summary

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The goal of this clinical research study is to find the highest tolerable dose of Abraxane® (nab-paclitaxel) when given directly into the liver, in combination with Gemzar® (gemcitabine) and Avastin® (bevacizumab) when given by vein.

Detailed Description

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The Study Drugs:

Nab-paclitaxel is designed to block cancer cells from dividing, which may cause the cancer cells to die.

Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die.

Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth, which may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of the combination of nab-paclitaxel and gemcitabine based on when you join this study. Up to 6 dose levels of nab-paclitaxel and gemcitabine will be tested. All participants will receive the same dose level of bevacizumab, regardless of when you join the study. Between 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of the combination of nab-paclitaxel and gemcitabine in combination with bevacizumab. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of nab-paclitaxel and gemcitabine given in combination with bevacizumab is found.

Once the highest tolerable dose is found, up to 12 additional participants receive this dose. This is called the expansion group.

Catheter Placement:

On Day 1 of each 21-day study cycle, a catheter (a sterile, flexible tube) will be placed into a large artery that carries blood to the liver in your groin area, on the right side of the body. The area where the catheter will be placed will first be numbed with local anesthetic. The catheter will be taped in place to prevent it from moving or coming out while you are receiving nab-paclitaxel. You will lie flat on your back while receiving the study drug, and you will be on bedrest until the catheter is removed.

The doctor who performs the catheter placement procedure will explain it to you in more detail, and you will be asked to sign a separate consent form that describes the catheter placement procedure and its risks in more detail.

After the catheter is in place, you will receive heparin, a drug that is used to help prevent blood clots. Heparin will be started as soon as the catheter is placed and will continue for up to 2 hours.

The catheter will be removed right after you receive nab-paclitaxel. While the catheter is being removed, the study staff will apply pressure to your groin area for 15 minutes in order to stop the bleeding. The catheter will be in place for about 1 hour, or until the nab-paclitaxel administration is complete.

Study Drug Administration:

Nab-paclitaxel will be given through the catheter into the artery that carries blood to your liver nonstop for 1 hour starting on Day 1 of each cycle. If the study doctor thinks it is needed, you will be given drugs by vein to lower the risk of nausea before each dose as part of your standard, routine care.

Gemcitabine will be given by vein over 1 hour on Days 1 and 8 of each cycle.

Bevacizumab will be given by vein on Day 1 of each cycle. The first time you receive bevacizumab, it will be given over 90 minutes. If you tolerate it well, the rest of the doses will be given over 30-60 minutes.

If you do not tolerate the study drug combination well, the doses that you receive may be lowered. If you experience certain side effects, the study drug doses may be delayed and that study cycle may last longer than 21 days.

Starting at least 24 hours after the you receive the study drug on Day 1, you will receive Neupogen® (filgrastim) through a needle injected under the skin. You will continue to receive filgrastim for 3 days (Days 2-4). Filgrastim is being given to help prevent possible side effects related to the other study drugs.

Study Visits:

You will stay in the hospital for up to 7 days (Days 1-7 of each cycle) at the beginning of each cycle, until you recover from any side effects that you may experience. You will be seen by a doctor or "advanced practice" nurse every day while you are in the hospital to check on how you are recovering.

On Day 1 of each cycle:

* You will have a physical exam, including measurement of your weight and vital signs.
* Blood (about 3 teaspoons) will be drawn for routine tests, to test your blood's ability to clot, and tumor marker testing.

On Day 2 of each cycle:

-You will have a physical exam, including measurement of your weight and vital signs.

Every 2 cycles, or at any time the study doctor thinks it is needed, women who are able to become pregnant will have a urine pregnancy test. To remain on this study, the pregnancy test must be negative.

At the end of every 2 cycles (Cycles 2, 4, 6, and so on), or at any time the study doctor thinks it is needed, a chest x-ray, CT scan, MRI scan, PET scan and/or PET/CT scan will be performed to check the status of the disease. After 10 cycles of study drug treatment, you may have scans every 3 cycles instead of 2 cycles, if your doctor feels that this is in your best interest. If the study doctor thinks it is better for you, other types of scans that have not been listed here may be performed.

Follow-Up Visit:

Six (6) weeks after the last dose of the study drug combination, or if you stop taking the study drug combination for any reason, the following tests and procedures will be performed:

* You will have a physical exam.
* Your performance status will be recorded.
* Blood (about 2 teaspoons) will be drawn for routine tests and to test your blood's ability to clot.
* If the study doctor thinks it is needed, a chest x-ray, CT scan, MRI scan, PET scan and/or PET/CT scan will be performed to check the status of the disease. If the study doctor thinks it is better for you, other types of scans that have not been listed here may be performed.

Length of Study:

You may continue taking the study drug combination for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

This is an investigational study. Nab-paclitaxel is FDA approved and commercially available when given by vein for the treatment of breast cancer.

Gemcitabine is FDA approved and commercially available for the treatment of pancreatic cancer, breast cancer that is metastatic (has spread to other parts of the body), non-small cell lung cancer (NSCL), and ovarian cancer. Bevacizumab is FDA approved and commercially available for the treatment of metastatic colorectal cancer, NSCL, and a type of brain cancer called glioblastoma multiforme.

Giving nab-paclitaxel into an artery that carries blood directly into the liver is investigational. Using the study drug combination for treating advanced cancer that has spread to the liver is investigational.

Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions

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Advanced Cancers

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HAI Abraxane + Gemcitabine + Bevacizumab

HAI (hepatic arterial infusions) Abraxane with Gemcitabine + Bevacizumab

Group Type EXPERIMENTAL

HAI Abraxane

Intervention Type DRUG

Starting dose: 120 mg/m\^2 by HAI infusion over 24 hours on Day 1 of 21 day cycle

Gemcitabine

Intervention Type DRUG

Starting dose: 600 mg/m\^2 by IV on Days 1 and 8 of 21 day cycle

Bevacizumab

Intervention Type DRUG

10 mg/kg IV on Day 1 of 21 day cycle

Filgrastim

Intervention Type DRUG

5 mcg/kg subcutaneously starting at least 24 hours after Day 1 completion of chemotherapy, for 3 days.

Interventions

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HAI Abraxane

Starting dose: 120 mg/m\^2 by HAI infusion over 24 hours on Day 1 of 21 day cycle

Intervention Type DRUG

Gemcitabine

Starting dose: 600 mg/m\^2 by IV on Days 1 and 8 of 21 day cycle

Intervention Type DRUG

Bevacizumab

10 mg/kg IV on Day 1 of 21 day cycle

Intervention Type DRUG

Filgrastim

5 mcg/kg subcutaneously starting at least 24 hours after Day 1 completion of chemotherapy, for 3 days.

Intervention Type DRUG

Other Intervention Names

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Nab-paclitaxel Paclitaxel (protein bound) ABI-007 Gemzar Gemcitabine Hydrochloride Avastin Anti-VEGF monoclonal antibody rhuMAb-VEGF G-CSF Neupogen

Eligibility Criteria

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Inclusion Criteria

1. Patients must have histologically confirmed cancer with metastatic liver metastases.
2. 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.
3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (capable of all self care but unable to carry out any work activities).
4. Adequate renal function (serum creatinine \</= 2.0 mg/dL or the calculated glomerular filtration rate (GFR) \>/= 40 mL/min if creatinine \> 2.0 mg/dL).
5. Hepatic function: Total bilirubin \</= 5 mg/dL, alanine transaminase (ALT) \</= 5 times upper normal reference value.
6. Adequate bone marrow function (absolute neutrophil count (ANC) \>/= 1500 cells/uL; platelets (PLT) \>/= 100,000 cells/uL).
7. 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.
8. 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.
9. Must be \>/= 18 years of age.

Exclusion Criteria

1. Pregnant females.
2. Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
3. Serious or non-healing wound, ulcer or bone fracture.
4. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
5. Uncontrolled systemic vascular hypertension (systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg).
6. 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.
7. Patients already in uncompensated liver failure (i.e. Child Pugh Liver Classification C).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Apostolia M. Tsimberidou, MD, PHD

Role: STUDY_CHAIR

UT MD Anderson Cancer Center

Locations

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UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

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NCI-2011-00555

Identifier Type: REGISTRY

Identifier Source: secondary_id

2009-0741

Identifier Type: -

Identifier Source: org_study_id