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Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01436227
Recruitment Status : Active, not recruiting
First Posted : September 19, 2011
Last Update Posted : October 18, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with von Hippel-Lindau syndrome. Pazopanib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Von Hippel-Lindau Syndrome Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride Phase 2

Detailed Description:


I. Evaluate safety and efficacy of treatment with pazopanib hydrochloride (pazopanib) for 6 months in patients with von Hippel-Lindau syndrome (VHL) who have a measurable VHL related lesion.


I. Evaluate rate of growth over time in target lesions before and after pazopanib treatment.

II. Evaluate need for surgical intervention over time in patients who receive pazopanib and compare to rate prior to receipt of drug.

III. Create an annotated tissue resource from patients with VHL for use in future research related to cancer.


I. Evaluate circulating factors in patients with VHL undergoing treatment with pazopanib.

II. Evaluate relationship between VHL genotype and response to pazopanib.


Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 4 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients benefitting from treatment may continue pazopanib hydrochloride in the absence of disease progression.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 24 weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome
Actual Study Start Date : January 17, 2012
Estimated Primary Completion Date : April 11, 2022
Estimated Study Completion Date : April 11, 2022

Arm Intervention/treatment
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 4 weeks for up to 24 weeks in the absence of disease progression or unacceptable toxicity. Patients benefitting from treatment may continue pazopanib hydrochloride in the absence of disease progression.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Pazopanib Hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient

Primary Outcome Measures :
  1. Overall response rate (complete response + partial response) [ Time Frame: At 24 weeks ]
    Determined by the Response Evaluation Criteria in Solid Tumors. Estimated with its corresponding 95% posterior credible interval.

  2. Progressive disease rate [ Time Frame: Up to 24 weeks ]
  3. Drug discontinuation due to toxicity [ Time Frame: Up to 24 weeks ]
  4. Time to progression (TTP) [ Time Frame: Up to 24 weeks ]
    TTP will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between prognostic groups. Regression analyses of survival data based on the Cox proportional hazards model will be conducted on TTP. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure that the models are appropriate.

Other Outcome Measures:
  1. Genetic mutations, discrete markers, and continuous biomarkers [ Time Frame: Up to 24 weeks ]
    Summary statistics, including frequency tabulation, means, standard deviations, median, and range, will be used to describe subject characteristics and marker data. The chi-squared test or Fisher's exact test will be used to test the association between two categorical variables, such as response and prognostic factors and discrete markers. The association among various continuous and discrete markers and response may be assessed first by the exploratory data analysis graphically and tested using Wilcoxon rank sum test.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Genetically confirmed diagnosis of VHL or measurable disease consistent with the clinical diagnosis of VHL
  • 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 likely etiology and natural history in the setting of a positive genetic test

    • Brain: asymptomatic hemangioblastoma, >= 0.5 cm
    • Spine: asymptomatic hemangioblastoma, >= 0.5 cm
    • Renal: solid mass suspicious for renal cell carcinoma (RCC) >= 1 cm or cystic mass (Bosniak 3-4) >= 1 cm
    • Pancreas: solid mass >= 1 cm and =< 3 cm suspicious for neuroendocrine tumor, or neuroendocrine tumor > 3 cm but not considered operable
    • Eye: asymptomatic peripapillary and/or macular hemangioblastoma, any size
    • Adrenal: asymptomatic or controlled pheochromocytoma greater than 1 cm in size
  • Patients may have received prior VHL-related systemic therapy, provided not within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
  • Absolute neutrophil count (ANC) >= 1.5 X 10^9/L
  • Hemoglobin >= 9 g/dL (5.6 mmol/L)

    • Subjects may not have had a transfusion within 7 days of screening assessment
  • Platelets >= 100 X 10^9/L
  • Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 X upper limit of normal (ULN)

    • Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation or if they are on low molecular weight heparin
  • Activated partial thromboplastin time (aPTT) =< 1.2 X ULN
  • Total bilirubin =< 1.5 X ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.0 X ULN

    • Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted
  • Serum creatinine =< 2.0 mg/dL (133 umol/L) OR, if > 2.0 mg/dL: calculated creatinine clearance (ClCR) >= 50 mL/min
  • Urine protein to creatinine ratio (UPC) < 1

    • If UPC >= 1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value < 1 g to be eligible
  • A female is eligible to enter and participate in this study if she is of: non-childbearing potential including

    • Any female who has had a surgical procedure rendering her incapable of becoming pregnant
    • Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L)
    • Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT; childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

      • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product
      • Oral contraceptive
      • Injectable progestogen
      • Implants of levonorgestrel
      • Estrogenic vaginal ring
      • Percutaneous contraceptive patches
      • Intrauterine device (IUD)
      • Male partner sterilization
      • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository); female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug

Exclusion Criteria:

  • Prior malignancy. Subjects who have had another non VHL related malignancy and have been disease-free for 2 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

    • Active peptic ulcer disease
    • Known intraluminal metastatic lesion/s with risk of bleeding
    • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel
  • Presence of uncontrolled infection
  • Corrected QT interval (QTc) > 480 msecs using Bazett's formula
  • History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Coronary artery bypass graft surgery
    • Symptomatic peripheral vascular disease
    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Poorly controlled hypertension (defined as systolic blood pressure [SBP] of >= 140 mmHg or diastolic blood pressure [DBP] of >= 90 mmHg); Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/DBP values from each BP assessment must be < 140/90 mmHg in order for a subject to be eligible for the study
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months; Note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
  • Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
  • Evidence of active bleeding or bleeding diathesis
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  • Unable or unwilling to discontinue use of prohibited medications list for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
  • Treatment with any of the following anti-cancer therapies:

    • Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
    • Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
  • Any ongoing toxicity from prior investigational therapy that is > grade 1 and/or that is progressing in severity, except alopecia

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01436227

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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Eric Jonasch M.D. Anderson Cancer Center
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01436227    
Other Study ID Numbers: 2011-0465
NCI-2011-03285 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2011-0465 ( Other Identifier: M D Anderson Cancer Center )
First Posted: September 19, 2011    Key Record Dates
Last Update Posted: October 18, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Von Hippel-Lindau Disease
Pathologic Processes
Neurocutaneous Syndromes
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn