Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

March 9, 2021 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TKI258
Drug: TKI258

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258
Time Frame: end of dose escalation
end of dose escalation
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
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)
Time Frame: every 8 weeks
every 8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
Time Frame: PK run day 1 & 2, cycle 1 day 2, 15, 28, cycle 2+ day 28, end of study
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
Time Frame: baseline, cycle 1 day 15, end of study
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
Time Frame: baseline, cycle 1 day 15, cycle 2 day 28
baseline, cycle 1 day 15, cycle 2 day 28
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
baseline, cycle 1 day 2 and cycle 2 day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2006

Primary Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

March 14, 2006

First Submitted That Met QC Criteria

March 15, 2006

First Posted (Estimate)

March 16, 2006

Study Record Updates

Last Update Posted (Actual)

March 11, 2021

Last Update Submitted That Met QC Criteria

March 9, 2021

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTKI258A2105

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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