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A Phase I Study of Hepatic Arterial Infusion (HAI) of Abraxane in Combination With Gemcitabine and Bevacizumab for Patients With Advanced Cancers Metastatic to the Liver


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Advanced Cancers

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Trial Information

A Phase I Study of Hepatic Arterial Infusion (HAI) of Abraxane in Combination With Gemcitabine and Bevacizumab for Patients With Advanced Cancers Metastatic to the Liver


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.


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 /= 40
mL/min if creatinine > 2.0 mg/dL).

5. Hepatic function: Total bilirubin 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).

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Time Frame:

Continous reassessment with every 21 day cycle

Safety Issue:

Yes

Principal Investigator

Apostolia M. Tsimberidou, MD, PHD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0741

NCT ID:

NCT01057264

Start Date:

January 2010

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Liver
  • Cancer
  • Hepatic arterial infusion
  • HAI
  • Abraxane
  • Nab-Paclitaxel
  • Paclitaxel
  • ABI-007
  • Gemcitabine
  • Gemcitabine Hydrochloride
  • Gemzar
  • Bevacizumab
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Filgrastim
  • G-CSF
  • Neupogen
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030