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A Phase 1 Trial of Vandetanib (a Multi-kinase Inhibitor of EGFR, VEGFR and RET Inhibitor) in Combination With Everolimus (an mTOR Inhibitor) in Advanced Cancer


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

Thank you

Trial Information

A Phase 1 Trial of Vandetanib (a Multi-kinase Inhibitor of EGFR, VEGFR and RET Inhibitor) in Combination With Everolimus (an mTOR Inhibitor) in Advanced 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 vandetanib and everolimus based on when you join this study. Up
to 5 dose levels of vandetanib and everolimus will be tested. Up to 3 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 at the lower dose. This will continue until the highest
tolerable dose of the combination of vandetanib and everolimus is found.

Study Drug Administration:

You will take the study drugs by mouth 1 time every day. The number of pills you will be
taking each day will depend on which dose level you are in. The study staff will tell you
how many pills you will take and will give you detailed directions on how and when to take
the study drugs.

Everolimus should be taken with about a cup (8 ounces) of water, with or without food.
Swallow everolimus whole. Do not chew, break, or crush everolimus, unless you cannot
swallow it whole. In this case, crush the everolimus tablet and mix it with 2 tablespoons
of water if you are not able to swallow it whole.

Vandetanib can be taken with or without food. Do not chew, crush, or break vandetanib.
Vandetanib can be swallowed whole OR you can mix vandetanib with water. To do this, mix the
pill(s) with 1/4 cup of water for 10 minutes and then drink; then rinse the cup with ½ cup
more water and drink.

Study Visits:

At all study visits, you will be asked about any drugs you may be taking and if you have had
any side effects.

Within 14 days before Cycle 1:

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

- Your performance status will be recorded.

- If it has been more than 3 days since your screening tests, blood (about 2 teaspoons)
and urine will be collected for routine tests.

At Weeks 2 and 4 of Cycle 1:

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

- Your performance status will be recorded.

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

Before Cycle 2 and then before every cycle after that:

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

- Your performance status will be recorded.

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

- Blood (about 1 ½ teaspoon) will be drawn to test your blood sugar.

- You will have an ECG (every 2 cycles).

Before Cycle 3, and then before every odd numbered cycle after that (Cycles 5, 7, and so
on):

- Blood (about 2-5 teaspoons) will be drawn to test for fat and sugar levels in the
blood. You will need to fast (not eat or drink anything but water) for at least 4
hours before this blood draw.

- You will have an x-ray, CT scan, PET scan, or MRI scan to check the status of the
disease.

- If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine
pregnancy test.

Length of Study:

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

You may choose to stop taking the study drugs at any time. You should tell the study staff
or doctor right away if you are thinking about stopping your participation in this study.
The study staff or doctor will talk to you about how to safely stop taking the study drugs.
You may be asked to return for a follow up visit to check if any side effects happen to you.

End-of-Study Visit:

If the study doctor thinks it is needed, you may have an end-of-study visit between 14 and
28 days after your last dose of study drugs. The following tests and procedures will be
performed:

- You will be asked about any drugs that you may be taking and if you have any side
effects.

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

- Your performance status will be recorded.

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

- You may have an electrocardiogram (ECG).

- If you are able to become pregnant will have a blood (about 1 teaspoon) or urine
pregnancy test.

This is an investigational study. Vandetanib is FDA-approved and commercially available for
the treatment of medullary thyroid carcinoma. Everolimus is FDA-approved and commercially
available for the treatment of pancreatic neuroendocrine tumor, subependymal giant cell
astrocytoma, and renal cell carcinoma. The use of these drugs in combination for the
treatment of advanced cancer is investigational.

Up to 118 patients will take part in this multicenter study. 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 who have no standard therapy available that
improves survival by at least three months.

2. Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy.
Patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their
previous targeted or biologic therapy; In addition, patients must be at least 3 weeks
beyond the last session of radiation therapy. Local palliative radiation therapy that
is not delivered to all target lesions is allowed immediately before or during
treatment.

3. The Eastern Cooperative Oncology Group (ECOG) performance status should be less or
equal to 3

4. Patients must have organ and marrow function defined as: Absolute neutrophil count
more or equal to 750/mL; platelets more or equal to 50,000/mL; creatinine less or
equal to 3 times upper limits of normal (ULN); total bilirubin less than or equal to
3.0.

5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence).

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, uncontrolled
infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.

2. Pregnant or lactating women.

3. History of hypersensitivity to vandetanib, lactose, murine products, or any component
of the formulation.

4. History of hypersensitivity to sirolimus, temsirolimus, everolimus.

5. History of hypersensitivity to any component of the formulation.

6. Patients unwilling or unable to sign informed consent document.

7. Presence of cardiac disease that, in the opinion of the Investigator, increases the
risk of ventricular arrhythmia.

8. History (within the last 3 months) or presence of stroke/cerebrovascular accident.

9. Congenital long QT syndrome.

10. QTcF interval greater than 500 ms that is not correctable to less than 500ms such as
with cessation of a causative medication, etc.

11. History of myocardial infarction within 6 months with a residual arrhythmia that in
the opinion of the Investigator, increases the risk of ventricular arrhythmia.

12. Presence of a symptomatic bradyarrhythmia or uncompensated heart failure.

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) of Vandetanib with Everolimus

Outcome Description:

Maximum tolerated dose (MTD) defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. MTD defined by DLTs that occur in first 28-day cycle (induction phase).

Outcome Time Frame:

28 days

Safety Issue:

No

Principal Investigator

Vivek Subbiah, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0953

NCT ID:

NCT01582191

Start Date:

May 2012

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Advanced Cancers
  • Advanced solid cancer
  • Metastatic cancer
  • Vandetanib
  • ZD 6474
  • Zactima
  • Caprelsa
  • Everolimus
  • Afinitor
  • RAD001
  • Multi-kinase Inhibitor
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030