Clinical Trials /

Pazopanib in Von Hippel-Lindau (VHL) Syndrome

NCT01436227

Description:

The goal of this clinical research study is to learn if pazopanib can help to control Von Hippel-Lindau Syndrome VHL. The safety of this drug will also be studied. This is an investigational study. Pazopanib is FDA approved and commercially available for kidney cancer. Its use to treat VHL is investigational. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Pazopanib will be provided at no cost to you during this study. Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Related Conditions:
  • Von Hippel-Lindau Syndrome
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pazopanib in Von Hippel-Lindau (VHL) Syndrome
  • Official Title: A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome

Clinical Trial IDs

  • ORG STUDY ID: 2011-0465
  • SECONDARY ID: NCI-2011-03285
  • NCT ID: NCT01436227

Conditions

  • Von Hippel-Lindau Syndrome

Interventions

DrugSynonymsArms
PazopanibGW786034Pazopanib

Purpose

The goal of this clinical research study is to learn if pazopanib can help to control Von Hippel-Lindau Syndrome VHL. The safety of this drug will also be studied. This is an investigational study. Pazopanib is FDA approved and commercially available for kidney cancer. Its use to treat VHL is investigational. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Pazopanib will be provided at no cost to you during this study. Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Detailed Description

      Study Groups and Study Drug Administration:

      If you are found to be eligible to take part in this study, you will take pazopanib by mouth
      1 time every day, at about the same time each day, at least 1 hour before or 2 hours after a
      meal.

      If you have any side effects from the drug, tell the study doctor right away. The study
      doctor may then lower the dose or keep the dose level the same.

      Each study cycle is 4 weeks.

      Study Visits:

        -  Your medical history will be recorded.

        -  You will have a physical exam, including measurement of your vital signs and weight.

        -  You will be asked about any drugs or treatments you may be receiving.

        -  Your performance status will be recorded.

      Every 2 weeks (for the first 8 weeks) and then once every cycle, blood (about 3 teaspoons)
      will be drawn for routine tests.

      Every 12 weeks (+/-7 days):

        -  Your medical history will be recorded.

        -  You will have a physical exam, including measurement of your vital signs and weight.

        -  Your performance status will be recorded.

        -  You will be asked about any drugs or treatments you may be receiving and any side
           effects that you have had.

      At the end of Cycles 3 and 6 and then every 12 weeks:

        -  You will have CT scans and MRI scans to check the status of the disease.

        -  If the doctor thinks it is needed, you will have an eye exam.

      Length of Study:

      You may receive treatment on this study for up to 24 weeks (6 cycles). If your doctor thinks
      you are benefitting, you may continue on study. You will no longer be able to take the study
      drug if the disease gets worse, intolerable side effects occur, or if you are unable to
      follow study directions.

      Your participation on the study will be over once you have completed the end-of-study visit
      and follow-up.

      Early Withdrawal/End-of-Study Visit:

      If you leave the study for any reason, the following tests will be performed.

        -  You will have a physical exam.

        -  Your performance status will be recorded.

        -  You will be asked about any drugs or treatments you may be receiving and any side
           effects that you have had.

        -  Blood (about 3 teaspoons) will be drawn for routine tests.

        -  You will have CT scans and MRI scans to check the status of the disease.

        -  If the doctors thinks it is needed, you will have an eye exam.

      Long-Term Follow-up:

      After you are off-study, the study staff will collect information about how you are doing
      either by checking your medical record or by calling you. If you are called, it will be about
      30 days after the last dose and then about every 3 months for up to 24 weeks. Each call
      should only last about 5 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
PazopanibExperimental800 mg by mouth once daily for up to six, four week cycles.
  • Pazopanib

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2

          3. Genetically confirmed diagnosis of VHL or measurable disease consistent with the
             clinical diagnosis of VHL. (Please refer to criterion #5)

          4. Measurable disease criteria: 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. a.) Brain: asymptomatic
             hemangioblastoma, >/= 0.5 cm ; b) Spine: asymptomatic hemangioblastoma, >/= 0.5 cm ;
             c) Renal: solid mass suspicious for RCC >/= 1 cm or cystic mass (Bosniak 3-4) >/= 1
             cm. ; d) Pancreas: solid mass >/= 1cm and </= 3 cm suspicious for neuroendocrine
             tumor, or neuroendocrine tumor > 3 cm but not considered operable. ; e) Eye:
             asymptomatic peripapillary and/or macular hemangioblastoma, any size ; f) Adrenal:
             asymptomatic or controlled pheochromocytoma greater than 1cm in size

          5. 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.

          6. Adequate organ system function as defined: a) Absolute neutrophil count (ANC) >/= 1.5
             X 10^9/L ; b) Hemoglobin >/= 9 g/dL (5.6 mmol/L) ; c) Platelets >/= 100 X 10^9/L ; d)
             Prothrombin time (PT) or international normalized ratio (INR) </= 1.2 X ULN ; e)
             Activated partial thromboplastin time (aPTT) </= 1.2 X ULN ; f) Total bilirubin </=
             1.5 X ULN ; g) Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)
             </= 2.0 X ULN ; h) Serum creatinine </= 2.0 mg/dL (133 µmol/L) Or, if >2.0 mg/dL:
             Calculated creatinine clearance (ClCR) (appropriate appendix) >/= 50 mL/min ; i) Urine
             Protein to Creatinine Ratio (UPC; appropriate appendix) <1

          7. A female is eligible to enter and participate in this study if she is of:
             Non-childbearing potential including a) any female who has had a surgical procedure
             rendering her incapable of becoming pregnant. ; b) 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). ; c) 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.

          8. # 8 Cont.) GSK acceptable contraceptive methods, when used consistently and in
             accordance with both the product label and the instructions of the physician, are as
             follow:a) 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. b) Oral contraceptive c) Injectable progestogen.
             d) Implants of levonorgestrel. e) Estrogenic vaginal ring f) Percutaneous
             contraceptive patches g) Intrauterine device (IUD) h) Male partner sterilization i)
             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:

          1. Prior malignancy. Note: 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.

          2. Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding including, but not limited to: a) Active peptic ulcer
             disease ; b) Known intraluminal metastatic lesion/s with risk of bleeding ; c)
             Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other
             gastrointestinal conditions with increased risk of perforation ; d) History of
             abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28
             days prior to beginning study treatment.

          3. Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational product including, but not limited to: a) Malabsorption syndrome ; b)
             Major resection of the stomach or small bowel.

          4. Presence of uncontrolled infection

          5. Corrected QT interval (QTc) > 480 msecs using Bazett's formula

          6. History of any one or more of the following cardiovascular conditions within the past
             6 months: a) Cardiac angioplasty or stenting ; b) Myocardial infarction ; c) Unstable
             angina ; d) Coronary artery bypass graft surgery ; e) Symptomatic peripheral vascular
             disease ; f) Class III or IV congestive heart failure, as defined by the New York
             Heart Association (NYHA)

          7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >/= 140
             mmHg or diastolic blood pressure (DBP) of >/= 90mmHg]. Note: Initiation or adjustment
             of antihypertensive medication(s) is permitted prior to study entry. 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 (see Section
             3.0. for details on BP control and re-assessment prior to study enrollment).

          8. 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

          9. 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).

         10. Evidence of active bleeding or bleeding diathesis

         11. 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.

         12. 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.

         13. Treatment with any of the following anti-cancer therapies: a) radiation therapy,
             surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR ;
             b) 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

         14. Any ongoing toxicity from prior investigational therapy that is >Grade 1 and/or that
             is progressing in severity, except alopecia
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:RECIST Overall Response (OR) Rate = Number of Participants with Complete Response and Partial Response (CR+PR) at 24 weeks
Time Frame:24 weeks
Safety Issue:
Description:Modified Response Evaluation Criteria in Solid Tumors (RECIST), evaluation of target lesions (organ-specific). Complete Response (CR): Disappearance all target lesions; Partial Response (PR): > 30% decrease in sum longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): > 20% increase in sum LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1 or > new lesions; Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum LD since treatment started.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Von Hippel-Lindau Syndrome
  • VHL
  • Von Hippel-Lindau related lesion
  • Pazopanib
  • GW786034

Last Updated

May 10, 2019