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

NCT00330564 | Terminated Phase 2 Results

• 1 other identifier: 2005-0463
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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)

Conditions

Von Hippel-Lindau Syndrome; Renal Cell Carcinoma; Hemangioblastoma

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

Outcome Measures

Primary Outcomes (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.

  12 weeks

Secondary Outcomes (1)

• Number of VHL Lesion Complete + Partial Responses

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

Study Arms (1)

SU011248 (Sutent, Sunitinib Malate)

EXPERIMENTAL

50 mg/day orally for 4 weeks

Drug: SU011248

Interventions

SU011248 DRUG

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

Also known as: Sunitinib Malate, Sutent

SU011248 (Sutent, Sunitinib Malate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Pfizer: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 22105611 RESULT

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

von Hippel-Lindau Disease; Carcinoma, Renal Cell; Hemangioblastoma; Cysts; Neoplasms

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Hemangioma, Capillary; Hemangioma; Neoplasms, Vascular Tissue; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Limitations include the conclusion of the study before maximum enrollment and the use of archival tissue that was not related to the participants in the clinical trial.

Results Point of Contact

• Title: Quality Assurance Specialist
• Organization: UT MD Anderson Cancer Center

caperez@mdanderson.org

713-563-1602

Study Officials

• Eric Jonasch, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: May 1, 2006
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 27, 2024
• Results First Posted: June 30, 2011

Record last verified: 2024-06

Locations

US (1)