Nab-paclitaxel, Gemcitabine, and Bevacizumab in Advanced Malignancies

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of a combination of nab-paclitaxel, gemcitabine, and bevacizumab based on when you
joined this study. All participants will receive the same dose level of gemcitabine. However,
the first group of participants will receive the lowest dose level of nab-paclitaxel and
bevacizumab. Each new group will receive a higher dose for one of the drugs than the group
before it, if no intolerable side effects were seen. The other drug may be at the same dose
or a lower dose. This will continue until the highest tolerable dose of combination of
nab-paclitaxel, gemcitabine, and bevacizumab is found. Up to 15 dose levels of the study drug
combination will be tested. Three (3) to 4 participants will be enrolled at each dose level.

Once the highest tolerated dose is found, up to 10 more participants will be added at that
dose level. This is called an expansion group.

Study Drug Administration:

On Days 1, 8, and 15 of each 28-day cycle, you will receive nab-paclitaxel and gemcitabine by
vein over about 90 minutes total. Also, if the first dose is well tolerated, you may be given
the remaining doses of nab-paclitaxel and gemcitabine at home.

On Days 1 and 15 of each cycle, you will receive bevacizumab by vein over about 60 minutes.
Also, if the first dose is well tolerated, you may be given the remaining doses of
bevacizumab at home.

Study Visits:

Each week during Cycle 1:

- Your medical history will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- Blood (about 2-5 teaspoons) will be drawn to test for fat levels in the blood. You will
need to fast for at least 4 hours before this blood draw.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects from
them.

- You will have urine tests performed to check for high levels of protein in your urine (a
known side effect of bevacizumab).

On Day 1 and 8 of Cycle 1, you will have a physical exam, including measurement of your
weight and vital signs.

During Week 1 of Cycles 2 and beyond:

- Your medical history will be recorded.

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

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- Blood (about 2-5 teaspoons) will be drawn to test for fat levels in the blood. You will
need to fast for at least 4 hours before this blood draw.

- Blood (about 2 teaspoons) will be drawn to see how well your blood clots and how long it
takes for your blood to clot.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects from
them.

- Females who are able to become pregnant must have a negative blood (about 1 teaspoon)
pregnancy test.

During Weeks 2 and 4 of Cycles 2 and beyond:

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects from
them.

- Blood (about 2 teaspoons) will be collected for routine tests.

During Week 3 of Cycles 2 and beyond:

- Your medical history will be recorded.

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

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- Blood (about 2-5 teaspoons) will be drawn to test for fat levels in the blood. You will
need to fast for at least 4 hours before this blood draw.

- Blood (about 2 teaspoons) will be drawn to see how well your blood clots and how long it
takes for your blood to clot.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and if you had any side effects from
them.

At the end of every 2 cycles (Cycles 2, 4, 6, and so on), you will have an x-ray, CT scan,
PET scan, or MRI scan to check the status of the disease. If you have disease in your bones,
a bone scan may also be done.

Length of Study:

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

You may chose to stop taking the study drugs at any time. You should tell the study doctor
right away if you are thinking about stopping your participation in this study. The study
doctor will talk to you about how to safely stop taking the study drugs.

This is an investigational study. Gemcitabine is FDA approved and commercially available for
the treatment of certain types of breast cancer, non-small cell lung cancer, pancreatic
cancer, and ovarian cancer. Bevacizumab is FDA approved and commercially available for the
treatment of colorectal, breast, lung, and brain cancer. Nab-paclitaxel is FDA approved and
commercially available for the treatment of breast cancer. The combination of these drugs is
investigational.

Up to 120 patients will take part in this study, but this may be increased at a later time.
All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with advanced or metastatic cancer that is refractory to standard therapy,
relapsed after standard therapy, or have no standard therapy that induces a CR rate of
at least 10% or improves survival by at least three months.

2. Patients should be at least four weeks from the last day of therapeutic radiation or
cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from
non-cytotoxic targeted or biologic therapy. Patients may have received palliative
radiation immediately before (or during) treatment provided radiation is not to the
only target lesion available.

3. ECOG performance status /= 60%).

4. Patients must have allowable organ and marrow function defined as: absolute neutrophil
count >/= 1,000/mL; platelets >/=50,000/mL; creatinine 350mg/dL; triglyceride level of no more than 400mg/dL.

5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days after the last dose.

6. Ability to understand and the willingness to sign a written informed consent document.

7. Patients may not be receiving any other investigational agents and/or any other
concurrent anticancer agents or therapies.

Exclusion Criteria:

1. Patients with hemoptysis within 28 days prior to entering the study.

2. Patients with clinically significant unexplained bleeding within 28 days prior to
entering the study.

3. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140mmHg,
diastolic blood pressure > 90 mmHg on medication).

4. Pregnant or lactating women.

5. History of hypersensitivity to bevacizumab, murine products, or any component of the
formulation.

6. History of hypersensitivity to gemcitabine.

7. History of hypersensitivity to nab-paclitaxel or paclitaxel.

8. Patients with clinically significant cardiovascular disease: Myocardial Infarction or
unstable angina pectoris within the last 6 months, Class III/IV NYHA heart failure.

9. History of CVA within 6 months.

10. History of surgery within last 28 days.

11. Grade 3/4 proteinuria.

12. Nephrotic syndrome.

13. Incompletely healed wound.