Pazopanib Hydrochloride in Treating Patients With Metastatic Melanoma That Cannot be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00861913
First received: March 13, 2009
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Drug: pazopanib hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Pazopanib (GW786034) in Pre-Treated and Untreated Metastatic Melanoma Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Tumor Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

    Tumor response rate is defined as the number of eligible patients whose disease status meets the Response Evaluation Criteria In Solid Tumors (RECIST) criteria for compete response (CR) or partial response (PR) divided by the number of evaluable patients. A ninety percent confidence interval for the true response proportion will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution and using the Duffy-Santner approach.

    Complete Response (CR): Disappearance of all target lesions.

    Partial Response (PR): At least a 30% decrease in the sum of the largest dimension (LD) of target lesions taking as reference the baseline sum LD.


  • Toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicity is defined as any grade 3 or higher adverse event as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and at least possibly related to treatment. The maximum grade for each type of toxicity will be recorded for each patient. We report the number of patients experiencing a grade 3 or higher adverse event at least possibly related to treatment.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Overall survival time is defined as the time from registration to the time of death due to any cause. Estimated using the method of Kaplan-Meier.

  • Progression Free Survival [ Time Frame: From registration to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    Progression free survival is defined as the time from registration to the time of progression or death, whichever occurs first. Estimated using the method of Kaplan-Meier.

  • Duration of Response [ Time Frame: From time of documented response to the date progression is documented, assessed up to 5 years. ] [ Designated as safety issue: No ]
    The date at which the objective status is first noted to be either a Complete Response (CR) or Partial Response (PR) to the date progression is documented, assessed up to 5 years.


Enrollment: 13
Study Start Date: April 2009
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)
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.
Drug: pazopanib hydrochloride
Given orally
Other Names:
  • GW786034B
  • Votrient
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the anti-tumor activity and safety profile of single agent Pazopanib (pazopanib hydrochloride).

SECONDARY OBJECTIVES:

I. To assess the impact of Pazopanib on circulating levels of vascular endothelial growth factor (VEGF).

II. To examine the association between tumor response and B-Raf and N-Ras mutations.

III. To examine pre/post-treatment expression levels of VEGF, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and Ki67.

IV. To correlate baseline and changes in p-ERK levels in the tumor with response.

V. To determine pazopanib steady-state trough plasma concentrations (Css,min) and the relationships between Css,min and the PD effects and toxicities of pazopanib.

VI. To examine the associations of common polymorphisms in CYP1A2, CYP2C8, UGT1A1, ABCB1, and ABCG2 with the PK and PD of pazopanib.

VII. To Assess Progression Free Survival. VIII. To Assess Overall Survival.

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

Inclusion Criteria:

  • 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
  • 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 reasonably be expected to limit compliance with study requirements
  • 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
  • No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00861913

Locations
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Amy Weise Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00861913     History of Changes
Other Study ID Numbers: NCI-2009-01163, NCI-2009-01163, CDR0000637188, MAYO-MC0875, MC0875, 8218, N01CM62205, P30CA015083
Study First Received: March 13, 2009
Results First Received: November 7, 2013
Last Updated: June 9, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 09, 2014