AzTrials
AzTrials

MelanomaPhase 1/2NCT00303251

Safety of TKI258 in Advanced/Metastatic Melanoma Subjects

A Phase 1/2 study testing TKI258 in people with Melanoma, run by Novartis Pharmaceuticals at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
TKI258
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
3 sitesUnited States
Study dates
Apr 2006to Sep 2009
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • MD Anderson Cancer

    Houston, Texas, 77030

  • James Graham Brown Cancer Center

    Louisville, Kentucky, 40202

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

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

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
Being tested
TKI258
Keywords
Locally Advanced or Metastatic Melanoma
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TKI258Drug

Study groups in NCT00303251
Study groupRoleWhat they receive
TKI258ExperimentalNot described
Receives: Drug: TKI258

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: end of dose escalation

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

    Measured: 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)

    Measured: every 8 weeks

Secondary outcomes (5)

  1. Assess the safety profile of TKI258 in this patient population

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: baseline, cycle 1 day 15, cycle 2 day 28

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

    Measured: baseline, cycle 1 day 2 and cycle 2 day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionSep 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00303251
Sponsor's protocol ID
CTKI258A2105
Status last verified
Feb 2013
First submitted
14 Mar 2006
Last updated
11 Mar 2021
Results posted
No

Publications

  • 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.

    PubMed 23400739

  • 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.

    PubMed 21976540

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TKI258 in people with Melanoma, run by Novartis Pharmaceuticals at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Expansion: Determine the maximum tolerated dose based on dose limiting toxicity of TKI258 (time frame: end of dose escalation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00303251, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in