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Pazopanib in Treating Patients With Metastatic Melanoma That Cannot be Removed by Surgery
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2009
First Received: March 13, 2009   Last Updated: April 14, 2009   History of Changes
Sponsors and Collaborators: Mayo Clinic
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00861913
  Purpose

RATIONALE: Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying the side effects of pazopanib and to see how well it works in treating patients with metastatic melanoma that cannot be removed by surgery.


Condition Intervention Phase
Melanoma (Skin)
Drug: pazopanib hydrochloride
Genetic: DNA analysis
Genetic: gene expression analysis
Genetic: mutation analysis
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Phase II

MedlinePlus related topics: Cancer Melanoma Surgery
Drug Information available for: Pazopanib Pazopanib Hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Trial of Pazopanib (GW786034) in Pre-Treated and Untreated Metastatic Melanoma Patients

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Survival [ Designated as safety issue: No ]
  • Time-to-disease progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time-to-treatment failure [ Designated as safety issue: No ]
  • Association between biomarkers and clinical benefit [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: April 2009
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess the anti-tumor activity and safety profile of single-agent pazopanib hydrochloride when administered to patients with pretreated or untreated metastatic melanoma.

Secondary

  • To assess the impact of pazopanib hydrochloride on circulating levels of VEGF.
  • To examine the association between tumor response and B-Raf and N-Ras mutations.
  • To examine pre- and post-treatment expression levels of VEGF, VEGFR-1, VEGFR-2, VEGFR-3, and Ki67.
  • To correlate baseline and changes in p-ERK levels in the tumor with response in these patients.
  • To determine pazopanib hydrochloride steady-state trough plasma concentrations ©_ss,min) and the relationships between C_ss,min and the pharmacodynamic effects and toxicities of pazopanib hydrochloride.
  • To examine the associations of common polymorphisms in CYP1A2, CYP2C8, UGT1A1, ABCB1, and ABCG2 with the pharmacokinetic and pharmacodynamics of pazopanib hydrochloride.
  • To assess progression-free survival of these patients.
  • To assess overall survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue biopsy at baseline and blood sample collection at baseline and on days 14, 28, and 42 for research studies. Tumor tissue samples are analyzed by DNA sequencing, ELISA, western blotting, and immunoperoxidase staining. Blood samples are analyzed for pharmacodynamics, pharmacokinetics, and pharmacogenetics by high-performance liquid chromatography with tandem mass spectrometry.

After completion of study treatment, patients are followed periodically for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed unresectable malignant melanoma

    • Radiographic or clinical evidence of metastatic disease
  • Measurable disease with ≥ 1 lesion whose longest diameter can be measured as ≥ 2.0 cm by CT or MRI scans or ≥ 1.0 cm by spiral CT scan

    • Disease that is measurable by physical examination only is not allowed
  • No known intraluminal metastatic lesion(s) with suspected bleeding
  • No brain metastases by MRI or CT scan

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelets ≥ 100,000/μL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Serum troponin normal
  • Urine protein ≤ 1+ (≤ 30 mg/dL) on 2 consecutive dipstick or other urine assessments taken ≥ 1 week apart
  • QTc interval < 480 msec
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
  • No serious nonhealing wound, ulcer, or bone fracture
  • No history of abdominal fistula, gastrointestinal perforation, active diverticulitis, intra-abdominal abscess, or gastrointestinal tract bleeding within the past 28 days
  • No history of myocardial infarction, cardiac arrhythmia within the past 6 months
  • No NYHA class III-IV heart failure

    • Patients with a history of class II heart failure and who are asymptomatic on treatment may be eligible
  • No history of bleeding disorder, including hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
  • No uncontrolled infection
  • No evidence of active bleeding or bleeding diathesis
  • No hemoptysis within 6 weeks of first dose of study drug
  • No active peptic ulcer disease
  • No inflammatory bowel disease
  • No ulcerative colitis or other gastrointestinal conditions with increased risk of perforation
  • No history of cerebrovascular accident, including transient ischemic attack, pulmonary embolism, or untreated deep venous thrombosis within the past 6 months

    • Patients with recent deep vein thrombosis who have been treated with therapeutic anticoagulating agents within the past 6 weeks are eligible
  • No known endobronchial lesions or involvement of large pulmonary vessels by tumor
  • No current active hepatic or biliary disease, except Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease
  • No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg and diastolic BP > 90 mm Hg)
  • No condition that impairs ability to swallow and retain pazopanib hydrochloride (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonablely be expected to limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • No admission for unstable angina, cardiac angioplasty, or stenting within the past 6 months
  • More than 6 weeks since prior major surgery
  • More than 4 weeks since prior and no concurrent radiotherapy
  • At least 14 days or 5 half-lives and no concurrent CYP interactive medications
  • No prior radiotherapy to ≥ 25% of bone marrow
  • No prior therapy with a VEGFR tyrosine-kinase inhibitor
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride
  • No concurrent chemotherapy
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00861913

Locations
United States, District of Columbia
Howard University Cancer Center Recruiting
Washington, District of Columbia, United States, 20060
Contact: Clinical Trials Office - Howard University Cancer Center     202-806-9122        
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
United States, Minnesota
CCOP - Metro-Minnesota Recruiting
St. Louis Park, Minnesota, United States, 55416
Contact: Thomas T. Amatruda, MD     952-993-1517        
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations     507-538-7623        
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Recruiting
Saint Louis, Missouri, United States, 63110-4803
Contact: Gerald P. Linette, MD, PhD     314-747-7222        
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Recruiting
Madison, Wisconsin, United States, 53792-6164
Contact: Clinical Trials Office - University of Wisconsin Paul P. Carbo     608-262-5223        
Australia, New South Wales
Sydney Cancer Centre at Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia, 2050
Contact: Anne Hamilton, MD, FRACP     61-2-9515-5894        
Australia, Western Australia
Sir Charles Gairdner Hospital - Nedlands Recruiting
Perth, Western Australia, Australia, 6009
Contact: Michael Millward, MD     61-8-9346-3823     millward@cyllene.uwa.edu.au    
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Amy Weise, DO Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Mayo Clinic Cancer Center ( Charles Erlichman )
Study ID Numbers: CDR0000637188, MAYO-MC0875
Study First Received: March 13, 2009
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00861913     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma
recurrent melanoma

Study placed in the following topic categories:
Neuroectodermal Tumors
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Nevus
Recurrence
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:
Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neuroendocrine Tumors
Melanoma

ClinicalTrials.gov processed this record on May 07, 2009