Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Von Hippel-Lindau Syndrome

Thank you

Trial Information

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


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:

On Day 1 of Cycle 1:

- 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 for an extra 18 cycles. 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.

This is an investigational study. Pazopanib is FDA approved and commercially available for
kidney cancer. Its use to treat VHL is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.


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
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 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) Activated partial thromboplastin time (aPTT) 1.5 X ULN ; g) Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)
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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

RECIST Overall Response (OR) Rate = Number of Participants with Complete Response and Partial Response (CR+PR) at 24 weeks

Outcome 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.

Outcome Time Frame:

24 weeks

Safety Issue:

No

Principal Investigator

Eric Jonasch, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0465

NCT ID:

NCT01436227

Start Date:

January 2012

Completion Date:

Related Keywords:

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

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030