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A Pilot Trial of TKI 258 (Dovitinib) in Von Hippel-Lindau Syndrome


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Von Hippel-Lindau Syndrome

Thank you

Trial Information

A Pilot Trial of TKI 258 (Dovitinib) in Von Hippel-Lindau Syndrome


The Study Drug:

Dovitinib is designed to perform several anti-tumor functions, including cutting off the
blood supply to tumors.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 5 dovitinib
capsules by mouth each day on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle.

You should take the dovitinib capsules with about a cup (8 ounces) of water and at least 1
hour before breakfast or at least 2 hours following breakfast.

If you have any side effects from the drug, tell the study doctor right away. The study
doctor may then lower the dose or keep the dose level the same.

If you miss a dose of dovitinib on Days 1-4 (or 8-11, 15-18, or 22-25), you should not make
up the dose on the same day. You should continue taking the drug as scheduled the following
day. If you miss a dose on Day 5 (or 12, 19, or 26), you should skip the dose, rest 2 days,
and begin dosing again as scheduled on Day 8 (or 15, 22, or 1 of the next cycle). The study
doctor will tell you about any additional steps that should be taken if you miss a dose.

Every 4 weeks on this study is called a study "cycle."

Study Visits:

On Day 1 of Cycle 1, you will have an ECG.

On Day 14 (+/- 3 days) of Cycles 1 and 2:

-Blood (about 3 teaspoons) will be drawn for routine tests. This blood testing may be done
at your local doctor's office and faxed to MD Anderson. You will be provided instructions
about how to fax laboratory test results.

On Day 1 of Cycles 3 and Beyond (+/- 3 days), blood (about 3 teaspoons) will be drawn for
routine tests.

Every 8 weeks (+/- 3 days):

- Any changes to your medical history since your last visit will be recorded.

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

- You will be asked about any drugs or treatments you may be receiving.

- Your performance status will be recorded.

- You will be asked about any side effects that you have had since your last visit.

At the End of Cycles 2 and 4:

- You will have CT scans and MRI scans to check the status of the disease.

- If the doctors know or suspect that VHL is affecting your eyes, you will have an eye
exam.

Length of Study:

You may continue taking the study drugs for as long as you are benefiting. You will be
taken off study if the disease gets worse or intolerable side effects occur.

Early Withdrawal /End of Treatment Visit:

About 30 days after you stop taking study drug, you will have the following procedures:

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

- Your performance status will be recorded.

- You will be asked about any drugs or treatments you may be receiving.

- You will be asked about any side effects that you may have had since your last visit.

- Blood (about 3 teaspoons) will be drawn for routine tests.

- You will have CT scans and MRI scans to check the status of the disease.

- If the doctors know or suspect that VHL is affecting your eyes, you will have an eye
exam.

About 24 weeks after your last dose of study drug, you will have the following procedures:

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

- You will have follow-up imaging scans to check the status of the disease.

- Blood (about 3 teaspoons) will be collected for routine tests.

- You will be asked about any drugs or treatments you may be receiving.

- You will be asked about any side effects that you may have had since your last visit.

This is an investigational study. Dovitinib is not FDA approved or commercially available.
It is currently being used for research purposes only.

Up to 25 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients must have genetically confirmed Von Hippel-Lindau (VHL) disease or patients
with a clinical diagnosis of VHL.

2. At least one of the following measurable hemangioblastomas which is undergoing
surveillance and the patient is not at immediate risk of needing intervention for
this or other lesions. a.) Brain: asymptomatic hemangioblastoma, > 0.5 cm; b.) Spine:
asymptomatic hemangioblastoma, > 0.5 cm; c.) Renal: solid mass suspicious for RCC
>/=1 cm or cystic mass >/=1 cm; d.) Pancreas: solid mass >/=1cm and < 3 cm suspicious
for neuroendocrine tumor; e.) Eye: asymptomatic peripapillary and/or macular
hemangioblastoma, any size f. Adrenal: Pheochromocytoma greater than 1cm in size.
NOTE: Biopsy is not required given the known natural history in the setting of a
positive genetic test.

3. Allowable prior therapy: a.) Patients having undergone prior therapy for VHL lesions
may enroll as long as other criteria are met. Previously radiated lesions may not be
considered as target lesions unless they demonstrate unequivocal evidence of growth;
b.) Major surgery, chemotherapy or radiation therapy completed > 4 weeks prior to
starting the study treatment.

4. Age >/= 18 years. Because no dosing or adverse event data are currently available on
the use of dovitinib in patients < 18 years of age, children are excluded from this
study but will be eligible for future pediatric single-agent trials, if applicable

5. ECOG performance status
6. Patients must have normal organ and marrow function as defined below: a.) Serum
aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and
serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) local laboratory upper limit of normal (ULN) are due to underlying malignancy; b.)
Total serum bilirubin /= 1500/mcL;
d.) Platelets >/=100,000/mcL; e.) Hemoglobin >/= 9.0 g/dL; f.) Serum creatinine < 1.5
x ULN; g) WBC >/= 3,000/mcl

7. Males (that have not been sterilized) and females of childbearing potential (female
that has not be amenorrheic for at least 1 year or that has not surgically
sterilized) must agree to use double-barrier birth control or abstinence while on the
protocol treatment

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

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to starting
study treatment or those who have not recovered ( to agents administered more than 4 weeks earlier.

2. Patients may not be receiving any other investigational agents.

3. Patients with any metastatic disease of any kind.

4. NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.

5. Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism.

6. Ongoing cardiac dysrhythmias of NCI CTCAE grade >/= 2.

7. Prolonged QTc interval on baseline EKG > 470ms.

8. Hypertension that cannot be controlled by medications (>140/90 mm Hg despite optimal
medical therapy).

9. LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever
is higher) or multiple gated acquisition scan ( MUGA) < 45% or lower limit of normal
(whichever is higher).

10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

11. Pregnant women are excluded from this study because dovitinib has the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
dovitinib, breastfeeding should be discontinued if the mother is treated with
dovitinib.

12. Known HIV-positive patients taking combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with dovitinib. Appropriate
studies will be undertaken in patients receiving combination antiretroviral therapy
when indicated.

13. Women of child-bearing potential, who are biologically able to conceive, not
employing two forms of highly effective contraception. Highly effective contraception
(e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device)
must be used by both sexes during the study and must be continued for 8 weeks after
the end of study treatment. Oral, implantable, or injectable contraceptives may be
affected by cytochrome P450 interactions, and are therefore not considered effective
for this study. Women of child-bearing potential, defined as sexually mature women
who have not undergone a hysterectomy or who have not been naturally postmenopausal
for at least 12 consecutive months (e.g., who has had menses any time in the
preceding 12 consecutive months), must have a negative serum pregnancy test days prior to starting study treatment.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Safety of Dovitinib for 6 months in VHL patients with measurable hemangioblastoma undergoing surveillance

Outcome Description:

Safety of treatment with dovitinib for 6 months in patients with VHL who have a measurable hemangioblastoma undergoing surveillance evaluated by toxicity scored using Common Toxicity Criteria (CTC) Version 4.0.

Outcome Time Frame:

Every 2 cycles (approximately 8 weeks) for 6 months

Safety Issue:

Yes

Principal Investigator

Eric Jonasch, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2010-0650

NCT ID:

NCT01266070

Start Date:

November 2012

Completion Date:

Related Keywords:

  • Von Hippel-lindau Syndrome
  • VHL
  • Hemangioblastoma
  • Tumor of the central nervous system
  • TKI258
  • Von Hippel-Lindau Disease

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030