TKI 258 in Von Hippel-Lindau Syndrome (VHL)
This study is currently recruiting participants.
Verified November 2013 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: December 22, 2010
Last updated: November 18, 2013
Last verified: November 2013
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.
Von Hippel-Lindau Syndrome
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Pilot Trial of TKI 258 (Dovitinib) in Von Hippel-Lindau Syndrome
Primary Outcome Measures:
Secondary Outcome Measures:
- Number of VHL Patients with Response at 6 Months [ Time Frame: Every 2 cycles (approximately 8 weeks) for 6 months ] [ Designated as safety issue: No ]
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.
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||November 2015 (Final data collection date for primary outcome measure)
500 mg/day on a 5 day on, 2 day off schedule
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).
Other Name: TKI258
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266070
|Contact: Eric Jonasch, MD
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
|Principal Investigator: Eric Jonasch, MD |
M.D. Anderson Cancer Center
||Eric Jonasch, MD
||UT MD Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 22, 2010
||November 18, 2013
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Tumor of the central nervous system
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 09, 2013
Von Hippel-Lindau Disease
Nervous System Diseases