Study of Sunitinib in Patients With Von Hippel-Lindau (VHL) Disease

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Brief Title

Study of Sunitinib in Patients With Von Hippel-Lindau (VHL) Disease

Official Title

A Single-arm, Phase II Study of Sunitinib in Patients With Von Hippel-Lindau (VHL) Disease

Brief Summary

      VHL patients may benefit from sunitinib. This study will investigate the following objectives
      :

      PRIMARY OBJECTIVE

        -  To determine the objective response rate according to RECIST criteria, in VHL patients
           with advanced tumors or tumors untreatable by other means, and treated with sunitinib.

      SECONDARY OBJECTIVES

        -  To evaluate the safety and tolerability of sunitinib in VHL patients according to the
           NCI-CTC criteria Version 3.0.

        -  To determine the following time-to-event endpoints: overall survival, time to disease
           progression, progression free survival, time to response and duration of response.

        -  To evaluate quality of life in VHL patients receiving sunitinib.
    

Detailed Description

      Treatment with sunitinib, 50 mg PO daily, 6 weeks courses with schedule 4/2 (4 weeks of
      treatment followed by 2 weeks of rest).

      Treatment until disease progression or unacceptable toxicity.

      Dose reduction depending on type and severity of toxicity. At the end of treatment period
      (after 8 courses), responding and well tolerating patients will be allowed to receive
      sunitinib upon investigator's opinion.

      Follow-up for up to 24 months from inclusion.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response rate (RECIST criteria)

Secondary Outcome

 Safety and tolerability (NCI-CTC criteria Version 3.0).

Condition

Von Hippel-Lindau Disease

Intervention

Sunitinib


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

5

Start Date

March 2010

Completion Date

February 2011

Primary Completion Date

February 2011

Eligibility Criteria

        INCLUSION CRITERIA

          1. Patients must have genetically or clinically confirmed VHL disease and have symptoms
             from VHL that are no longer controllable by conventional approaches.

          2. Patients must have at least one of the following lesions :

               -  Eye : retinal hemangioblastoma that can no longer be treated by laser therapy or
                  cryotherapy and resulting in progressive loss of vision;

               -  CNS : cerebellar, bulbar, spinal, or cerebellopontine angle haemangioblastoma or
                  endolymphatic sac tumor causing neurological symptoms that are not amenable to
                  further surgery, or have recurred after a first surgery;

               -  Kidney: multiple or bilateral tumors not accessible to conservative surgery, or
                  tumors having recurred after surgery and/or radiofrequency ablation or
                  advanced/metastatic RCC;

               -  Pancreas: inextirpable or advanced neuroendocrine tumors.

          3. Patients previously treated for VHL with surgery, chemotherapy or radiotherapy are
             considered eligible for this study under the condition that these treatments were
             completed more than 4 weeks prior starting the study treatment. Previously radiated
             lesions will be considered as target lesions only if they demonstrate unequivocal
             evidence of growth upon imagery.

          4. Male or female, at least 18 year-old.

          5. Performance status ECOG 0-2

          6. Life expectancy = 3 months

          7. Biological/clinical values within the following limits:

               -  Total serum bilirubin = 1.5 x ULN (patients with Gilbert's disease are not
                  eligible)

               -  Serum transaminases and alkaline phosphatases = 2.5 x ULN, or in case of
                  underlying malignancy (hepatic metastasis) = 5x ULN

               -  Serum creatinine = 1.5 x ULN, creatinine clearance = 80 ml/min

               -  Absolute neutrophil count = 1500/mm3

               -  Platelets = 100,000/mm3

               -  Hemoglobin = 9.0 g/dL

               -  QTc interval = 450 msec

               -  Left ventricular ejection fraction (LVEF) = lower limit of institutional normal
                  as assessed by multigated acquisition (MUGA) scan or echocardiogram

          8. Eligibility of patients receiving any medications or substances which may alter the
             activity or pharmacokinetics of sunitinib (CYP3A4 inhibitors or inducers among which
             ketoconazole, theophylline, phenobarbital, coumadin/warfarin) will be decided after
             review by the principal investigator of possibility to interrupt or switch to other
             medications. Otherwise, patient is not eligible. Anticoagulants drugs (among which
             coumadin/warfarin) may be, either switched to low-molecular-weight heparin, or be
             subject to individual dose adaptation in order to maintain INR in the target range
             with regard to patient's history, all along his participation in the study.

          9. Signed and dated informed consent document stating that the patient, or legally
             representative, has been informed of all the aspects of the trial prior to enrollment

         10. Willingness and ability to comply with all protocol assessments, schedule of visits,
             and procedures that are or could be requested as part of this study.

         11. Affiliated to French social security system

        EXCLUSION CRITERIA

          1. Chemotherapy, radiotherapy, radiofrequency or surgery within 4 weeks prior to entering
             the study or not complete recovering from adverse events due to drugs administered
             more than 4 weeks earlier.

          2. Patients receiving any other investigational agent or having participated in a
             clinical trial in the last 30 days.

          3. History of allergic reaction attributed to compounds of similar chemical or biological
             composition to sunitinib.

          4. Previous treatment with sunitinib

          5. NCI-CTCAE grade = 3 hemorrhage within 4 weeks prior to study entry.

          6. History of known or suspected brain metastases, spinal cord compression, carcinomatous
             meningitis, evidence of leptomeningeal disease (excepted leptomeningeal
             hemangioblastoma, according to the neurologist) on screening CT scan or MRI.

          7. Any of the following within the 6 months prior to study drug administration:
             symptomatic congestive heart failure, myocardial infarction or coronary artery bypass,
             pulmonary embolism, ongoing severe or unstable angina pectoris, NCI-CTCAE grade = 2
             cardiac dysrhythmia, cerebrovascular accident or transient ischemic attack.

          8. Hypertension >140/90 mmHg that cannot be controlled despite optimal antihypertensive
             therapy.

          9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
             the normal range despite medication.

         10. Other severe acute or chronic medical condition including (but not limited to),
             ongoing infection, unstable or uncompensated respiratory, cardiac, hepatic or renal
             disease, psychiatric condition, laboratory abnormality that would impart, in the
             judgment of the investigator, excess risk associated with study participation or study
             drug administration, or which would make the patient inappropriate for entry into the
             trial.

         11. Any medical condition (gastric or small intestine pathology, malabsorption syndrome)
             that might interfere with oral medication absorption.

         12. Known HIV-positive patients treated with antiretroviral therapy (potential
             pharmacokinetic interactions with sunitinib).

         13. Pregnancy or breastfeeding. Patients must agree to use effective contraception during
             the study, including oral contraceptives, intrauterine devices, or being unable to
             procreate.

         14. Any other malignancy within the last 3 years excepted basal cell carcinoma, in situ
             cervical carcinoma, squamous cell skin cancer, pT1/a bladder cancer with no evidence
             of recurrence during the last 12 months.
      

Gender

All

Ages

18 Years - 90 Years

Accepts Healthy Volunteers

No

Contacts

Stephane RICHARD, MD, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01168440

Organization ID

VHLSUT09



Study Sponsor

Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie


Study Sponsor

Stephane RICHARD, MD, PhD, Principal Investigator, Hôpital Kremlin-Bicêtre (France)


Verification Date

September 2012