Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow

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Brief Title

Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow

Official Title

A Phase 2 Study of SU011248 (Sunitinib Malate) in Von Hippel-Lindau Syndrome

Brief Summary

      The goal of this clinical research study is to learn if sunitinib malate (SU011248) can help
      to control VHL. The safety of this drug will also be studied.

      Primary objectives:

        -  Evaluate safety of treatment with SU011248/sunitinib malate (50 mg daily dose for 4
           weeks, then 2 weeks off) for 6 months in patients with Von Hippel-Lindau Syndrome (VHL)
           who have a measurable lesion undergoing surveillance

      Secondary objectives:

        -  Evaluate efficacy of treatment with SU011248/sunitinib malate (50 mg daily dose for 4
           weeks, then 2 weeks off) for 6 months in patients with VHL who have a measurable lesion
           undergoing surveillance

      Correlative objectives:

        -  Evaluate quality of life of SU011248/sunitinib malate therapy in VHL patients

        -  Evaluate peripheral blood lymphocyte receptor phosphorylation in VHL patients taking
           SU011248/sunitinib malate (optional procedure)

        -  Correlate results of dynamic contrast-enhanced and diffusion weighted MRI and dynamic
           contrast enhanced CT with response and explore findings suggestive of surrogates of
           early response (optional procedure)
    

Detailed Description

      Sunitinib malate is designed to block pathways that control important events such as the
      growth of blood vessels that are essential for the growth of cancer.

      Before you can start treatment on this study, you will have what are called "screening
      tests." These tests will help the doctor decide if you are eligible to take part in this
      study. You will have standard scans to check the status of your disease, including computed
      tomography (CT) scans of the chest and abdomen (stomach area) and/or a magnetic resonance
      imaging (MRI) scan of the spine, if you have lesions in these areas. You will have an
      electrocardiogram (ECG -- a test that measures the electrical activity of the heart) and an
      echocardiogram or MUGA scan (echocardiogram/MUGA scan - a test to determine how well your
      heart is functioning by measuring its ability to pump blood). If the doctors know or suspect
      that VHL is affecting your eyes you will have an eye exam performed.

      Your complete medical history will be recorded and you will have a physical exam, including
      measurement of your vital signs (blood pressure, heart rate, temperature, and breathing
      rate), height, and weight. You will be asked about any medications or treatments you are
      currently taking. Blood (about 2 teaspoons) will be drawn for routine tests. You will also be
      asked about your ability to perform daily activities. Women who are able to have children
      must have a negative blood pregnancy test.

      You will be asked to complete 2 questionnaires that ask about your quality of life and your
      level of fatigue. It will take about 20 minutes to complete both questionnaires. The same
      questionnaires will then be completed 4-6 weeks later, and again at the end of treatment.

      If you are found to be eligible to take part in this study, you will take sunitinib malate
      once a day, either with or without food. You will take the drug for 4 weeks in a row followed
      by 2 weeks of rest with no study drug. These 6 weeks are called a study "cycle".

      Before beginning each new cycle, you will have a physical exam and your complete medical
      history will be recorded. Blood (about 1 teaspoon) will be drawn for routine tests. You will
      be asked about any drugs you have taken and any side effects you may have experienced. You
      will also be asked about your ability to perform daily activities.

      At the end of Cycles 2 and 4, you will have CT or MRI scans to evaluate the status of your
      disease and eye exams may be repeated for those with known lesions on their eye(s).

      You may receive treatment on this study for 24 weeks. However if you are showing benefit from
      the study drug, you may continue on study for an additional 24 weeks. (maximum total of 48
      weeks) You will be taken off study if the disease gets worse or if intolerable side effects
      occur.

      Once you stop treatment, you will have an end-of-study visit. At this visit, you will have a
      physical exam and blood (about 1 teaspoon) will be drawn for routine tests. You will be asked
      about any medications you have taken and any side effects you may have experienced. You will
      have CT or MRI scans to evaluate the status of your disease, as well as an eye exam if your
      eyes are affected by your disease. If you have completed at least 1 cycle of treatment on
      this study, and have had imaging scans in the past 28 days, you will skip the end of study
      evaluation and return for the 48 week follow-up visit.

      You will have a follow-up visit about 48 weeks after your date of enrollment on this study.
      At this visit, you will have a physical exam and blood (about 1 teaspoon) will be drawn for
      routine tests. You will be asked about any medications you have taken and any side effects
      you may have experienced. You will have CT or MRI scans to evaluate the status of your
      disease. If your eyes are being affected by the disease, you will have a follow-up eye exam.

      Once you complete the 48 week follow-up visit, you are considered off-study.

      This is an investigational study. Sunitinib malate has been authorized by the FDA for
      research purposes only. About 28 patients will take part in this clinical research study. All
      will be enrolled at M. D. Anderson.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Safety of Sunitinib Administration in Participants With Von Hippel-Lindau Syndrome (VHL)

Secondary Outcome

 Number of VHL Lesion Complete + Partial Responses

Condition

Von Hippel-Lindau Syndrome

Intervention

SU011248

Study Arms / Comparison Groups

 SU011248 (Sutent, Sunitinib Malate)
Description:  50 mg/day orally for 4 weeks

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

15

Start Date

May 2006

Completion Date

May 2011

Primary Completion Date

May 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have genetically confirmed Von Hippel-Lindau (VHL) disease.

          -  At least one measurable VHL-related lesion, which is undergoing surveillance, and
             patient is not at immediate risk of needing intervention for this or other lesions.
             Biopsy is not required given the known natural history in the setting of a positive
             genetic test. (1) Renal: solid mass suspicious for Renal Cell Carcinoma (RCC) >/= 1 cm
             or cystic mass >/= 1 cm; (2) Pancreas: Solid mass >/= 1cm & < 3cm suspicious for
             neuroendocrine tumor; (3) Brain: asymptomatic hemangioblastoma > 5mm; (4) Spine:
             asymptomatic hemangioblastoma, > 1cm; (5) Eye: asymptomatic peripapillary and/or
             macular hemangioblastoma, any size.

          -  Allowable prior therapy: (1) 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;
             (2) Major surgery, chemotherapy or radiation therapy completed >4 weeks prior to
             starting the study treatment.

          -  Age >/= 18 years. Because no dosing or adverse event data are currently available on
             the use of SU011248/sunitinib malate in patients <18 years of age, children are
             excluded from this study but will be eligible for future pediatric single-agent
             trials, if applicable.

          -  Eastern Cooperative Oncology Group (ECOG) performance status /= 1500mcL; (4) Platelets >/= 100,000 mcL;
             (5) Hemoglobin >/= 9.0 g/dL; (6) Serum creatinine < 1.5 x UL.

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of SU011248/sunitinib
             malate as listed below will be determined following review of their case by the
             Principal Investigators. If possible, efforts will be made to switch motivated
             patients to other medications, otherwise patients will be excluded: (1) Ketoconazole,
             (2) Theophylline, (3) Phenobarbital, (4) Coumadin at therapeutic doses (low dose
             Coumadin up to 2 mg po daily for thromboprophylaxis is allowed).

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

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Patients may not be receiving any other investigational agents.

          -  Patients with any metastatic disease of any kind.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to SU011248/sunitinib malate.

          -  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
             grade 3 hemorrhage within 4 weeks of starting the study treatment.

          -  History of or known brain metastases, spinal cord compression, or carcinomatous
             meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening
             Computer tomography (CT) or Magnetic Resonance Imaging (MRI) scan.

          -  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.

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

          -  Prolonged QTc interval on baseline electrocardiogram (ECG or EKG)>470ms.

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

          -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range with medication.

          -  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.

          -  Pregnant women are excluded from this study because SU011248/sunitinib malate 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 SU011248/sunitinib malate, breastfeeding should be discontinued if the
             mother is treated with SU011248/sunitinib malate.

          -  Known HIV-positive patients taking combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with SU011248/sunitinib
             malate. Appropriate studies will be undertaken in patients receiving combination
             antiretroviral therapy when indicated.
      

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

NCT00330564

Organization ID

2005-0463


Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 Pfizer

Study Sponsor

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


Verification Date

February 2012