Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

NCT00303251 | Completed Phase 1

• 1 other identifier: CTKI258A2105
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

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.

Conditions

Melanoma

Keywords

Locally Advanced or Metastatic Melanoma

Outcome Measures

Primary Outcomes (3)

• Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258

  end of dose escalation

• Dose Expansion: Determine the plasma and whole blood pharmacokinetics of orally administered TKI258

  PK run-in days 1 & 2, cycle 1 days 1, 8, 15, 16, 28, cycle 2 day 15, cycle 2+ day 28

• Dose Escalation: Assess tumor response according to RECIST as measured by response rate and lack of early progressive disease (<=2 months)

  every 8 weeks

Secondary Outcomes (5)

• Assess the safety profile of TKI258 in this patient population

  PK run in day 1 & 2, cycle 1 day 8, 15, 28, cycle 2+ day 15 & 28, end of study

• Assess the effect of TKI258 on biomarkers in the blood

  PK run day 1 & 2, cycle 1 day 2, 15, 28, cycle 2+ day 28, end of study

• Assess biomarker changes in tumor/nevi biopsies and archival tumor tissues where accessible, pre- and post-treatment

  baseline, cycle 1 day 15, end of study

• Assess changes in tumor glucose metabolism/cell viability between pre- and post-treatment using [18F]-FDG-PET

  baseline, cycle 1 day 15, cycle 2 day 28

• Assess anti-angiogenic effects of TKI258 using DCE-MRI pre- and post-treatment

  baseline, cycle 1 day 2 and cycle 2 day 28

Study Arms (1)

TKI258

EXPERIMENTAL

Drug: TKI258

Interventions

TKI258 DRUG

TKI258

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Wang X, Kay A, Anak O, Angevin E, Escudier B, Zhou W, Feng Y, Dugan M, Schran H. Population pharmacokinetic/pharmacodynamic modeling to assist dosing schedule selection for dovitinib. J Clin Pharmacol. 2013 Jan;53(1):14-20. doi: 10.1177/0091270011433330. Epub 2013 Jan 24.

  PMID: 23400739 DERIVED

• Kim KB, Chesney J, Robinson D, Gardner H, Shi MM, Kirkwood JM. Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. Clin Cancer Res. 2011 Dec 1;17(23):7451-61. doi: 10.1158/1078-0432.CCR-11-1747. Epub 2011 Oct 5.

  PMID: 21976540 DERIVED

Related Links

• Results for (Study ID) from the Novartis Clinical Trials website

MeSH Terms

Conditions

Melanoma

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2006
• First Posted: March 16, 2006
• Study Start: April 1, 2006
• Primary Completion: September 1, 2009
• Last Updated: March 11, 2021

Record last verified: 2013-02

Locations

US (3)