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Von Hippel-Lindau SyndromePhase 2NCT01266070

TKI 258 in Von Hippel-Lindau Syndrome (VHL)

A Phase 2 study testing Dovitinib in people with Von Hippel-Lindau Syndrome, 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 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Von Hippel-Lindau Syndrome
What is being tested?
Dovitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
Nov 2012to Dec 2015
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 or patients with a clinical diagnosis of VHL.
  • 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.
  • 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.
  • 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
  • ECOG performance status </= 2
  • 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]) </=2.5 x local laboratory upper limit of normal (ULN) are due to underlying malignancy; b.) Total serum bilirubin </=1.5 x ULN; c.) Absolute neutrophil count (ANC) >/= 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
  • 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
  • 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 starting study treatment or those who have not recovered (</= Grade 1 )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.
  • NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
  • 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.
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  • Prolonged QTc interval on baseline EKG > 470ms.
  • Hypertension that cannot be controlled by medications (>140/90 mm Hg despite optimal medical therapy).
  • 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).
  • 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 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.
  • 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.
  • 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 </= 14 days prior to starting study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Dovitinib
Keywords
VHL, Hemangioblastoma, Tumor of the central nervous system, TKI258
Medical subject headings
von Hippel-Lindau Disease, Hemangioblastoma, Central Nervous System Neoplasms

What participants receive

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

  • DovitinibDrug

    Also called TKI258

    500 mg (5 capsules) daily by mouth on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle (i.e. 5 days on, 2 days off schedule).

Study groups in NCT01266070
Study groupRoleWhat they receive
DovitinibExperimental500 mg/day on a 5 day on, 2 day off schedule
Receives: Drug: Dovitinib

What is being measured

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

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

    Most frequent \& Most Serious Adverse Events: Safety of treatment with Dovitinib for 6 months in participants with VHL who have a measurable hemangioblastoma undergoing surveillance evaluated by toxicity scored using Common Toxicity Criteria (CTC) Version 4.0.

    Measured: Every 2 cycles (approximately 8 weeks) for 6 months

Secondary outcomes (1)

  1. Number of VHL Participants With Response at 6 Months

    Efficacy of treatment with dovitinib for 6 months in patients with VHL who have a measurable lesion evaluated by response using RECIST (Response Evaluation Criteria in Solid Tumors): Complete Response, Partial Response, Progressive Disease or Stable Disease.

    Measured: Every 2 cycles (approximately 8 weeks) for 6 months

Timeline

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

  1. First posted24 Dec 2010 (estimated)
  2. Study startNov 2012
  3. Primary completionDec 2015
  4. Study completionDec 2015

Why it stopped: Trial met toxicity stopping rule

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01266070
Sponsor's protocol ID
2010-0650
Other IDs
NCI-2011-00305
Status last verified
Dec 2015
First submitted
22 Dec 2010
Last updated
13 Feb 2017
Data monitoring committee
No

Publications

  • Larcher A, Rowe I, Belladelli F, Fallara G, Raggi D, Necchi A, Montorsi F, Capitanio U, Salonia A; OSR VHL Program. Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950.

    PubMed 34783716

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dovitinib in people with Von Hippel-Lindau Syndrome, 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 13 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 13 Feb 2017. 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 13 Feb 2017). 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?

Most Frequent & Most Serious Adverse Events: Safety of Dovitinib for 6 Months (time frame: Every 2 cycles (approximately 8 weeks) for 6 months). 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 NCT01266070, 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 13 Feb 2017.

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