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A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies


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

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Trial Information

A Phase I Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies


Study Drugs:

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for
tumor growth. This may prevent or slow the growth of cancer cells.

Vorinostat is designed to cause chemical changes in different groups of proteins that are
attached to DNA (the genetic material of cells), which may slow the growth of cancer cells
or cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, up to 12 dose levels of
pazopanib and vorinostat will be tested. Three (3) to 6 participants will be enrolled at
each dose level of the combination of pazopanib and vorinostat. The first group of
participants will receive the lowest dose level of pazopanib and vorinostat. Each new
group(s) will receive a higher combination dose of pazopanib and vorinostat than the group
before it, if no intolerable side effects were seen. Participants may be enrolled on 1-3
similar dose levels of pazopanib and vorinostat at the same time. You will be assigned to a
dose level based on when you joined this study. This will continue until the highest
tolerable dose(s) of the study drug combination is found.

The dose of the study drug combination that you receive may be lowered if you have
intolerable side effects.

Once the highest tolerable dose of pazopanib and vorinostat is found, this combination dose
will be given to an expansion group of 14 additional participants.

Study Drug Administration:

You will take pazopanib and vorinostat by mouth 1 time each day. Note that you will not
take the study drugs at the same time as each other. You should take pazopanib either 1
hour before or 2 hours after eating a meal. You should take vorinostat with food.

Study Visits:

Each study cycle is 28 days.

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

If you are able to take your blood pressure at home, you will be asked to take your blood
pressure each day while you are participating on this study.

Within 7 days before the first dose of study drugs:

- You will have a physical exam, including measurement of your weight and vital signs
(blood pressure, heart rate, temperature, and breathing rate).

- You will be asked how well you are able to perform the normal activities of daily
living (performance status).

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

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

Every week during Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests.

During Week 1 of each cycle:

- Your medical history will be recorded.

- 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.

At the end of Cycle 2 and then every 2-3 cycles after that:

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

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

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 be taken off study early if the disease gets worse, or you have
intolerable side effects.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At
this visit, the following tests and procedures performed:

- Your medical history will be recorded.

- 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.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

- If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or
PET scan to check the status of the disease.

This is an investigational study. Pazopanib is FDA approved and commercially available for
the treatment of renal cell carcinoma. Vorinostat is FDA approved and commercially
available for the treatment of T cell lymphoma. The combination of pazopanib and vorinostat
in advanced cancers is investigational.

Up to 120 evaluable patients will take part in this study. All will be enrolled at MD
Anderson.


Inclusion Criteria:



1. Patients with advanced cancer, either refractory to standard therapy or for which no
effective standard therapy that increases survival for at least 3 months is
available.

2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.

3. Men or women aged >/= 18 years. However, patients who are 13 years old or older and
have more than 45 kg of body weight will be eligible after consultation with their
pediatric attending since the doses of these agents are the fixed doses.

4. Women of child-bearing potential and men must agree to use adequate contraception.

5. ECOG performance status of 0 to 2.

6. Adequate organ functions: Neutrophils > 1000/uL, Platelets >/= 75,000/uL, Total
bilirubin liver metastases persist, Serum creatinine < 2 x ULN

7. Patients with either previous VEGF inhibition based treatment or previous vorinostat
based treatment are eligible. However, patients who received both VEGF and HDAC
inhibition simultaneously are ineligible.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring intravenous antibiotics, symptomatic congestive heart failure
(NYHA Class III or IV), or unstable angina pectoris.

2. Inadequately controlled hypertension (defined as systolic blood pressure >or = 140
and/or diastolic blood pressure > or = 90 mmHg on antihypertensive medications), any
prior history of hypertensive crisis or hypertensive encephalopathy, and history of
myocardial infarction or unstable angina within 6 months prior to study enrollment.

3. History of stroke or transient ischemic attack within 6 months prior to study
enrollment.

4. Major surgical procedure within 28 days prior to study enrollment.

5. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment.

6. History of allergic reactions to the study drugs, their analogs or any component of
the products.

7. Any treatment specific for tumor control within 3 weeks of study drugs; or within 2
weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or
mitomycin C), or within 5 half-lives for targeted agents with half lives and
pharmacodynamic effects lasting less than 5 days (that includes but is not limited to
erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents). Palliative
radiation immediately before or during the study is acceptable provided there is
evaluable disease that has not been radiated.

8. Urine for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on
urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate

9. Patients with clinical bleeding, active gastric or duodenal ulcer.

10. Symptomatic primary tumors or metastasis of brain and/or central nervous system that
are uncontrolled with antiepileptics and requiring high doses of steroids.

11. Concurrent use of antiarrythmics or contraindicated medications (including, but not
limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin,
thioridazine).

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 pazopanib and vorinostat

Outcome Time Frame:

With each first cycle (28 days)

Safety Issue:

Yes

Principal Investigator

Siqing Fu, MD,PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2011-0051

NCT ID:

NCT01339871

Start Date:

April 2011

Completion Date:

Related Keywords:

  • Advanced Cancer
  • Pazopanib
  • Vorinostat
  • Advanced Malignancies
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030