TKI 258 in Von Hippel-Lindau Syndrome (VHL)

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Brief Title

TKI 258 in Von Hippel-Lindau Syndrome (VHL)

Official Title

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

Brief Summary

      The goal of this clinical research study is to learn if dovitinib can safely be given to
      patients who have VHL with a measurable hemangioblastoma (tumor of the central nervous
      system). The effects of this drug on the disease will also be studied.
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Most Frequent & Most Serious Adverse Events: Safety of Dovitinib for 6 Months

Secondary Outcome

 Number of VHL Participants With Response at 6 Months

Condition

Von Hippel-Lindau Syndrome

Intervention

Dovitinib

Study Arms / Comparison Groups

 Dovitinib
Description:  500 mg/day on a 5 day on, 2 day off schedule

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

6

Start Date

November 2012

Completion Date

December 2015

Primary Completion Date

December 2015

Eligibility Criteria

        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 /= 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 (/= 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 					

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Eric Jonasch, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01266070

Organization ID

2010-0650

Secondary IDs

NCI-2011-00305

Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 Novartis

Study Sponsor

Eric Jonasch, MD, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

December 2015