Pazopanib in Von Hippel-Lindau (VHL) Syndrome

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Brief Title

Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome

Official Title

A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome

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.
    

Detailed 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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall response rate (complete response + partial response)


Condition

Von Hippel-Lindau Syndrome

Intervention

Laboratory Biomarker Analysis

Study Arms / Comparison Groups

 Treatment (pazopanib hydrochloride)
Description:  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.

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

Other

Estimated Enrollment

40

Start Date

January 17, 2012

Completion Date

April 11, 2021

Primary Completion Date

April 11, 2021

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
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Eric Jonasch, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01436227

Organization ID

2011-0465

Secondary IDs

NCI-2011-03285

Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Eric Jonasch, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

December 2020