Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

NCT01436227 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2011-0465NCI-2011-03285
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Von Hippel-Lindau Syndrome

Outcome Measures

Primary Outcomes (4)

• Overall Response Rate (Complete Response + Partial Response)

  Overall response rate (complete response + partial response) Determined by the Response Evaluation Criteria in Solid Tumors. Estimated with its corresponding 95% posterior credible interval.

  At 24 weeks

• Progressive Disease Rate

  Progressive disease rate

  Up to 24 weeks

• Drug Discontinuation Due to Toxicity

  Drug discontinuation due to toxicity

  Up to 24 weeks

• Time to Progression (TTP)

  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.

  Up to 24 weeks

Study Arms (1)

Treatment (pazopanib hydrochloride)

EXPERIMENTAL

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; Drug: Pazopanib Hydrochloride

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (pazopanib hydrochloride)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Jonasch E, McCutcheon IE, Gombos DS, Ahrar K, Perrier ND, Liu D, Robichaux CC, Villarreal MF, Weldon JA, Woodson AH, Pilie PG, Fuller GN, Waguespack SG, Matin SF. Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2018 Oct;19(10):1351-1359. doi: 10.1016/S1470-2045(18)30487-X. Epub 2018 Sep 17.

  PMID: 30236511 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

von Hippel-Lindau Disease

Interventions

pazopanib

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

Results Point of Contact

• Title: Eric Jonasch, MD
• Organization: M.D. Anderson Cancer Center

ejonasch@mdanderson.org

713-792-2830

Study Officials

• Eric Jonasch

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 19, 2011
• Study Start: January 17, 2012
• Primary Completion: March 13, 2024
• Study Completion: March 13, 2024
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-05

Locations

US (1)