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Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

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ClinicalTrials.gov Identifier: NCT00303251
Recruitment Status : Completed
First Posted : March 16, 2006
Last Update Posted : December 19, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This study is an open-label, dose-escalating study to delineate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TKI258. Pharmacokinetics and pharmacodynamics will be performed on all subjects. The eligible subject population consists of subjects who have been diagnosed with locally advanced or metastatic melanoma that is refractory to standard therapy or for which no curative standard therapy exists.

Condition or disease Intervention/treatment Phase
Melanoma Drug: TKI258 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of TKI258 (CHIR-258) in Patients With Locally Advanced or Metastatic Melanoma
Study Start Date : April 2006
Actual Primary Completion Date : September 2009

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: TKI258 Drug: TKI258


Outcome Measures
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Primary Outcome Measures :
  1. Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258 [ Time Frame: end of dose escalation ]
  2. Dose Expansion: Determine the plasma and whole blood pharmacokinetics of orally administered TKI258 [ Time Frame: PK run-in days 1 & 2, cycle 1 days 1, 8, 15, 16, 28, cycle 2 day 15, cycle 2+ day 28 ]
  3. Dose Escalation: Assess tumor response according to RECIST as measured by response rate and lack of early progressive disease (<=2 months) [ Time Frame: every 8 weeks ]

Secondary Outcome Measures :
  1. Assess the safety profile of TKI258 in this patient population [ Time Frame: PK run in day 1 & 2, cycle 1 day 8, 15, 28, cycle 2+ day 15 & 28, end of study ]
  2. Assess the effect of TKI258 on biomarkers in the blood [ Time Frame: PK run day 1 & 2, cycle 1 day 2, 15, 28, cycle 2+ day 28, end of study ]
  3. Assess biomarker changes in tumor/nevi biopsies and archival tumor tissues where accessible, pre- and post-treatment [ Time Frame: baseline, cycle 1 day 15, end of study ]
  4. Assess changes in tumor glucose metabolism/cell viability between pre- and post-treatment using [18F]-FDG-PET [ Time Frame: baseline, cycle 1 day 15, cycle 2 day 28 ]
  5. Assess anti-angiogenic effects of TKI258 using DCE-MRI pre- and post-treatment [ Time Frame: baseline, cycle 1 day 2 and cycle 2 day 28 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of locally advanced or metastatic melanoma (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC or IV) that is refractory to standard therapy or for which no curative standard therapy exists.
  • Measurable disease
  • Must be eighteen years of age or older
  • Must meet baseline laboratory requirements
  • ECOG performance status 0 or 1
  • Adults of reproductive potential must agree to use effective contraception or be sterile

Exclusion Criteria:

  • Concurrent therapy with any other investigational agent
  • Uncontrolled central nervous system metastases
  • Impaired cardiac function or clinically significant cardiac disease

  • Received

    • chemotherapy, targeted therapy or monoclonal antibody therapy ≤4 weeks
    • biological therapy or immunotherapy (therapeutic or diagnostic) ≤2 weeks
    • an investigational agent (therapeutic or diagnostic) ≤4 weeks prior to starting study drug or has not recovered from side effects of such therapy
  • Received any hematopoietic colony-stimulating factor (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin is allowed.
  • Has undergone major surgery ≤ 2 weeks prior to starting study drug or has not recovered from side effects of such surgery.
  • Malabsorption syndrome or uncontrolled gastrointestinal symptoms such as nausea, diarrhea, vomiting
  • Pregnant or breast feeding women
  • History of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Chronic anticoagulation therapy with full strength aspirin, Coumadin, or heparin.
  • History of thromboembolic or cerebrovascular events within the last 12 months.
  • History of rectal bleeding, bloody vomit, or spitting up blood within the last 3 months.
  • Known diagnosis of HIV infection (HIV testing is not mandatory)
  • Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort and quinidine is prohibited.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study-drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, make the patient inappropriate for this study
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00303251


Locations
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United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
MD Anderson Cancer
Houston, Texas, United States, 77030
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00303251    
Other Study ID Numbers: CTKI258A2105
First Posted: March 16, 2006    Key Record Dates
Last Update Posted: December 19, 2020
Last Verified: February 2013
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Locally Advanced or Metastatic Melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas