Von Hippel-Lindau Disease Clinical Trial

Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

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.

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Full Description

PRIMARY OBJECTIVE:

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.

SECONDARY OBJECTIVES:

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.

PRECLINICAL OBJECTIVES:

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

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

OUTLINE:

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.

View Eligibility Criteria

Eligibility Criteria

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

Study is for people with:

Von Hippel-Lindau Disease

Phase:

Phase 2

Estimated Enrollment:

32

Study ID:

NCT01436227

Recruitment Status:

Completed

Sponsor:

M.D. Anderson Cancer Center

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There is 1 Location for this study

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M D Anderson Cancer Center
Houston Texas, 77030, United States

How clear is this clinincal trial information?

Study is for people with:

Von Hippel-Lindau Disease

Phase:

Phase 2

Estimated Enrollment:

32

Study ID:

NCT01436227

Recruitment Status:

Completed

Sponsor:


M.D. Anderson Cancer Center

How clear is this clinincal trial information?

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