Pazopanib in Von Hippel-Lindau (VHL) Syndrome
This study is currently recruiting participants.
Verified December 2013 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: September 15, 2011
Last updated: December 30, 2013
Last verified: December 2013
The goal of this clinical research study is to learn if pazopanib can help to control VHL. The safety of this drug will also be studied.
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.
Von Hippel-Lindau Syndrome
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Trial of Pazopanib in Von Hippel-Lindau Syndrome
Primary Outcome Measures:
- RECIST Overall Response (OR) Rate = Number of Participants with Complete Response and Partial Response (CR+PR) at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
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.
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||January 2017 (Final data collection date for primary outcome measure)
800 mg by mouth once daily for a 4 week cycle.
800 mg by mouth once daily for a 4 week cycle.
Other Name: GW786034
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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. (Please refer to criterion #5)
- 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
- 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.
- 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
- 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 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.
- 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.
- 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.
- 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.
- 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: 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)
- 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).
- 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: 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
- Any ongoing toxicity from prior investigational therapy that is >Grade 1 and/or that is progressing in severity, except alopecia
Please refer to this study by its ClinicalTrials.gov identifier: NCT01436227
|Contact: Eric Jonasch, MD
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Eric Jonasch, MD
||UT MD Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||September 15, 2011
||December 30, 2013
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Von Hippel-Lindau Syndrome
Von Hippel-Lindau related lesion
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 06, 2014
Von Hippel-Lindau Disease
Nervous System Diseases