Von Hippel-Lindau SyndromePhase 2NCT01436227
Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome
A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Von Hippel-Lindau Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Von Hippel-Lindau Syndrome
- What is being tested?
- Laboratory Biomarker Analysis and Pazopanib Hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2012to 13 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Von Hippel-Lindau Syndrome
- Being tested
- Laboratory Biomarker Analysis, Pazopanib Hydrochloride
- Medical subject headings
- von Hippel-Lindau Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Pazopanib HydrochlorideDrug
Also called GW786034B, Votrient
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Laboratory Biomarker Analysis; Drug: Pazopanib Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 24 weeks
Progressive Disease Rate
Progressive disease rate
Measured: Up to 24 weeks
Drug Discontinuation Due to Toxicity
Drug discontinuation due to toxicity
Measured: 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.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2011 (estimated)
- Study start17 Jan 2012
- Primary completion13 Mar 2024
- Study completion13 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Von Hippel-Lindau SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Eric Jonasch, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01436227
- Sponsor's protocol ID
- 2011-0465
- Other IDs
- NCI-2011-03285, 2011-0465
- Status last verified
- May 2025
- First submitted
- 15 Sep 2011
- Last updated
- 2 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30236511
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome
- ClinicalTrials.gov ID
- NCT01436227
- Acronym / sponsor ID
- 2011-0465
- Conditions
- Von Hippel-Lindau Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 17 Jan 2012 (actual)
- Primary completion
- 13 Mar 2024 (actual)
- Study completion
- 13 Mar 2024 (actual)
- First posted
- 19 Sep 2011 (estimated)
- Results
- Posted 2 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pazopanib hydrochloride) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Pazopanib HydrochloridePatients 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (37 listed)
- 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
- 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
Key exclusion criteria (28 listed)
- 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:
- Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- Presence of uncontrolled infection
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pazopanib hydrochloride) |
| Pazopanib HydrochlorideAlso: GW786034B, VotrientGiven PO | Drug | Treatment (pazopanib hydrochloride) |
Primary outcome
Overall Response Rate (Complete Response + Partial Response)
Time frame: At 24 weeks
Overall response rate (complete response + partial response) Determined by the Response Evaluation Criteria in Solid Tumors. Estimated with its corresponding 95% posterior credible interval.
Progressive Disease Rate
Time frame: Up to 24 weeks
Progressive disease rate
Drug Discontinuation Due to Toxicity
Time frame: Up to 24 weeks
Drug discontinuation due to toxicity
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30236511Jonasch 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.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Jonasch principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Pazopanib Hydrochloride in people with Von Hippel-Lindau Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (Complete Response + Partial Response) (time frame: At 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01436227, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025.