- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00715182
A Phase I/II Study to Assess the Safety and Efficacy of TKI258 for the Treatment of Refractory Advanced/Metastatic Renal Cell Cancer
December 17, 2020 updated by: Novartis Pharmaceuticals
A Phase I/II Multi-center, Open Label Study of TKI258 Administered Orally on an Intermittent Schedule in Adult Patients With Advanced or Metastatic Renal Cell Cancer (RCC)
This is a phase I/II open-label study to delineate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of TKI258.
The eligible subject population consists of subjects who have been diagnosed with advanced or metastatic renal cell cancer 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)
87
Phase
- 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
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Bordeaux Cedex, France, 33075
- Novartis Investigative Site
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Villejuif Cedex, France, 94805
- Novartis Investigative Site
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Hannover, Germany, 30625
- Novartis Investigative Site
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München, Germany, 81675
- Novartis Investigative Site
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Rotterdam, Netherlands, 3075 EA
- Novartis Investigative Site
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Madrid, Spain, 28041
- Novartis Investigative Site
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Taichung, Taiwan, 40705
- Novartis Investigative Site
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Taipei, Taiwan, 10002
- Novartis Investigative Site
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Taiwan, ROC
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Taipei, Taiwan, ROC, Taiwan, 112
- Novartis Investigative Site
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California
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San Francisco, California, United States
- Novartis Investigative Site
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North Carolina
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Durham, North Carolina, United States, 27710
- Novartis Investigative Site
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Washington
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Seattle, Washington, United States, 98109-1023
- Novartis Investigative Site
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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:
- For phase I, confirmed advanced/ metastatic renal cell carcinoma for which no other therapeutic options exist.
- For phase II, must have been previously treated with VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib).
- For phase II, must have at least one measurable lesion at baseline.
- For both phase I & II, measurable histologically or cytology confirmed progressive metastatic renal cell carcinoma with predominant clear cell histology (>50%).
- At least 4 weeks must have elapsed since any prior anti-cancer therapy (6 weeks for nitrosoureas or mitomycin C).
- Must have recovered from adverse events (to grade 1 or less toxicity according to CTCAE 3.0) due to agents administered more than 28 days earlier.
- Must be eighteen years of age or older
- ECOG performance status 0 or 1.
- Must meet baseline laboratory requirement
- Life expectancy greater than or equal to 12 weeks.
- Signed and witnessed informed consent prior to any screening procedures.
Exclusion Criteria:
- Concurrent therapy with any other investigational agent within 28 days prior to baseline.
- Pregnant or breast feeding women.
- Clinically significant cardiac disease (New York Heart Association, Class III or IV) or impaired cardiac function or clinically significant cardiac diseases.
- Uncontrolled infection.
- Diabetes mellitus with signs of clinically significant peripheral vascular disease.
- Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month.
- Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, adrenal or thyroid glands.
- Prior acute or chronic pancreatitis of any etiology.
- Acute and chronic liver disease and all chronic liver impairment.
- Malabsorption syndrome or uncontrolled gastrointestinal symptoms (such as nausea, diarrhea and vomiting) with toxicity greater than NCI CTCAE grade 2.
- Other severe, acutem or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and, in the judgement of the investigator, would make the subject inappropriate for this study.
- Treatment with any of the medications that have a potential risk of prolonging the QT interval or inducing Torsades de Points and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
- Use of ketoconazole, erythromycin, carbamazapine, phenobarbital, rifampin, phenytoin and quinidine 2 weeks prior to baseline.
- Major surgery within 28 days prior to starting study drug or who have not recovered from side effects of such therapy.
- Known diagnosis of HIV infection (HIV testing is not mandatory).
- History of another clinically significant primary malignancy that requires active intervention.
- Patients with brain metastases as assessed by radiologic imaging.
- Alcohol or substance abuse disorder.
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 |
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Experimental: TKI258
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Phase I: To determine the MTD of TKI258, administered orally on a 5 days on/2 days off schedule to adult patients with advanced or metastatic RCC whose diseases have progressed despite standard therapy or for whom no standard anticancer therapy exists.
Time Frame: at end of phase I
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at end of phase I
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Phase II: To determine anti-tumor activity of TKI258 in advanced or metastatic RCC patients with predominant clear cell histology that have been previously treated with VEGF receptor tyrosine kinase inhibitor (sunitinib and/or sorafenib).
Time Frame: at end of phase II
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at end of phase II
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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To assess the safety profile of TKI258
Time Frame: cycle 1: day 1,8,15,26; cycle 2: day 15, 28; cycle 3+: day 28 & at end of study
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cycle 1: day 1,8,15,26; cycle 2: day 15, 28; cycle 3+: day 28 & at end of study
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To assess the effect of TKI258 on plasma biomarkers, pre- and post-treatment
Time Frame: cycle 1: day 1,15,26; cycle 2: 15 & 28; every other cycles: day 28 & at end of study
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cycle 1: day 1,15,26; cycle 2: 15 & 28; every other cycles: day 28 & at end of study
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To explore the pharmacokinetic and pharmacodynamic relationship
Time Frame: end of study
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end of study
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To characterize the single and multiple-dose PK profiles of oral TKI258
Time Frame: cycle 1: day 1, 8, 15 &26; cycle 2 & 3: day 15 & 28
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cycle 1: day 1, 8, 15 &26; cycle 2 & 3: day 15 & 28
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Progression free survival and over all survival
Time Frame: end of study
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end of study
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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
July 1, 2008
Primary Completion (Actual)
July 1, 2012
Study Completion (Actual)
July 1, 2012
Study Registration Dates
First Submitted
July 11, 2008
First Submitted That Met QC Criteria
July 14, 2008
First Posted (Estimate)
July 15, 2008
Study Record Updates
Last Update Posted (Actual)
December 21, 2020
Last Update Submitted That Met QC Criteria
December 17, 2020
Last Verified
January 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTKI258A2107
- 2007-004391-39 (EudraCT Number)
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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