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Von Hippel-Lindau SyndromePhase 2NCT00330564

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

A Phase 2 study testing SU011248 in people with Von Hippel-Lindau Syndrome and Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SU011248
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
May 2006to May 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 </= 2
  • Patients must have normal organ and marrow function as defined: (1) serum aspartate transaminase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase ([ALT]; serum glutamic pyruvic transaminase [SGPT]) </= 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT</= 5 x ULN if liver function abnormalities are due to underlying malignancy; (2) Total serum bilirubin </=1.5 x ULN; (3) Absolute neutrophil count (ANC) >/= 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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:

Read more
  • 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)
Read the 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.

Being tested
SU011248
Keywords
VHL Syndrome, Von Hippel-Lindau Syndrome, VHL Disease, Kidney, Retina, Brain, Spinal cord, Pancreas, Inner ear, Cysts, Tumors, Sunitinib Malate, SU011248, Sutent, VHL, Sunitinib, Renal cell carcinoma, Hemangioblastoma, Endothelium
Medical subject headings
von Hippel-Lindau Disease, Carcinoma, Renal Cell, Hemangioblastoma, Cysts, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SU011248Drug

    Also called Sunitinib Malate, Sutent

    50 mg/day orally for 4 weeks, no treatment for 2 weeks (6 weeks = 1 cycle).

Study groups in NCT00330564
Study groupRoleWhat they receive
SU011248 (Sutent, Sunitinib Malate)Experimental50 mg/day orally for 4 weeks
Receives: Drug: SU011248

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Safety evaluation = Number of participants with treatment terminating toxicity using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Early stopping rules applied when treatment terminating toxicity occurred in the first 6 week cycle. Recurring grade 3 toxicity requires dose reduction, with no more than 2 dose reductions permitted. If no improvement after 4 weeks, patient is taken off drug and off study, and the event recorded as treatment terminating toxicity.

    Measured: 12 weeks

Secondary outcomes (1)

  1. Number of VHL Lesion Complete + Partial Responses

    Response of VHL lesions (number) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) of Complete Response (CR): Disappearance of all target lesions, and Partial Response (PR): At least a 30% decrease in the sum of longest diameter (LD) of target lesions, reference baseline sum LD. Progressive Disease (PD): 20% increase in LD sum and Stable Disease (SD): Insufficient shrinkage to qualify for PR nor increase to qualify for PD. Degree and timing of response in affected organs evaluated in order to determine organ specific kinetics of therapy.

    Measured: Baseline to 12 months (evaluations at 6 and 12 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionMay 2011
  4. Study completionMay 2011

Why it stopped: Slow accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00330564
Sponsor's protocol ID
2005-0463
Status last verified
Jun 2024
First submitted
26 May 2006
Last updated
27 Jun 2024
Data monitoring committee
No

Publications

  • Jonasch E, McCutcheon IE, Waguespack SG, Wen S, Davis DW, Smith LA, Tannir NM, Gombos DS, Fuller GN, Matin SF. Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease. Ann Oncol. 2011 Dec;22(12):2661-2666. doi: 10.1093/annonc/mdr011.

    PubMed 22105611

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SU011248 in people with Von Hippel-Lindau Syndrome and Renal Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Sunitinib Administration in Participants With Von Hippel-Lindau Syndrome (VHL) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00330564, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2024.

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