Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow
This study has been terminated.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: May 26, 2006
Last updated: February 23, 2012
Last verified: February 2012
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.
- 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
- 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
- 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)
Von Hippel-Lindau Syndrome
Renal Cell Carcinoma
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 2 Study of SU011248 (Sunitinib Malate) in Von Hippel-Lindau Syndrome
Primary Outcome Measures:
- Safety of Sunitinib Administration in Participants With Von Hippel-Lindau Syndrome (VHL) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
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.
Secondary Outcome Measures:
- Number of VHL Lesion Complete + Partial Responses [ Time Frame: Baseline to 12 months (evaluations at 6 and 12 months) ] [ Designated as safety issue: No ]
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.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||May 2011 (Final data collection date for primary outcome measure)
Experimental: SU011248 (Sutent, Sunitinib Malate)
50 mg/day orally for 4 weeks
50 mg/day orally for 4 weeks, no treatment for 2 weeks (6 weeks = 1 cycle).
|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.
- 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.
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00330564
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Eric Jonasch, MD
||M.D. Anderson Cancer Center
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 26, 2006
|Results First Received:
||June 1, 2011
||February 23, 2012
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Von Hippel-Lindau Syndrome
Renal cell carcinoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 28, 2014
Von Hippel-Lindau Disease
Nervous System Diseases
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Vascular Tissue
Angiogenesis Modulating Agents
Physiological Effects of Drugs