Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00303251
First received: March 14, 2006
Last updated: February 9, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Melanoma
Drug: TKI258
Phase 1
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: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258 [ Time Frame: end of dose escalation ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: April 2006
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TKI258 Drug: TKI258

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT00303251

Locations
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
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00303251     History of Changes
Other Study ID Numbers: CTKI258A2105
Study First Received: March 14, 2006
Last Updated: February 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Locally Advanced or Metastatic Melanoma

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

ClinicalTrials.gov processed this record on October 21, 2014