Advanced/ Metastatic Renal Cell CancerPhase 1NCT00715182
A Phase I/II Study to Assess the Safety and Efficacy of TKI258 for the Treatment of Refractory Advanced/Metastatic Renal Cell Cancer
A Phase 1 study testing TKI258 in people with Advanced/ Metastatic Renal Cell Cancer, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/ Metastatic Renal Cell Cancer
- What is being tested?
- TKI258
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 12 sitesin 6 countries
- Study dates
- Jul 2008to Jul 2012
- Phase
- Phase 1
- 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
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 6 countries.
12 sites in 6 countries
United States3 sites
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
San Francisco, California
Novartis Investigative Site
Seattle, Washington, 98109-1023
Taiwan3 sites
Novartis Investigative Site
Taichung, 40705
Novartis Investigative Site
Taipei, Taiwan, ROC, 112
Novartis Investigative Site
Taipei, 10002
France2 sites
Novartis Investigative Site
Bordeaux, 33075
Novartis Investigative Site
Villejuif, 94805
Germany2 sites
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
München, 81675
About this study
Official title: 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.
- Conditions
- Advanced/ Metastatic Renal Cell Cancer
- Being tested
- TKI258
- Keywords
- Renal Cell Cancer
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKI258Drug
| Study group | Role | What they receive |
|---|---|---|
| TKI258 | Experimental | Not described Receives: Drug: TKI258 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at end of phase I
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).
Measured: at end of phase II
Secondary outcomes (5)
To assess the safety profile of TKI258
Measured: cycle 1: day 1,8,15,26; cycle 2: day 15, 28; cycle 3+: day 28 & at end of study
To assess the effect of TKI258 on plasma biomarkers, pre- and post-treatment
Measured: cycle 1: day 1,15,26; cycle 2: 15 & 28; every other cycles: day 28 & at end of study
To explore the pharmacokinetic and pharmacodynamic relationship
Measured: end of study
To characterize the single and multiple-dose PK profiles of oral TKI258
Measured: cycle 1: day 1, 8, 15 &26; cycle 2 & 3: day 15 & 28
Progression free survival and over all survival
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/ Metastatic Renal Cell CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00715182
- Sponsor's protocol ID
- CTKI258A2107
- Other IDs
- 2007-004391-39
- Status last verified
- Jan 2013
- First submitted
- 11 Jul 2008
- Last updated
- 21 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT00715182
- Acronym / sponsor ID
- CTKI258A2107
- Conditions
- Advanced/ Metastatic Renal Cell Cancer
- Keywords
- Renal Cell Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 15 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TKI258 | Experimental | Drug: TKI258 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TKI258 | Drug | TKI258 |
Primary outcome
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
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
5 secondary outcomes
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
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
To explore the pharmacokinetic and pharmacodynamic relationship
Time frame: end of study
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
Progression free survival and over all survival
Time frame: end of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Results for CTKI258A2107 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TKI258 in people with Advanced/ Metastatic Renal Cell Cancer, run by Novartis Pharmaceuticals at 12 sites in 6 countries.
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 11 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 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Taiwan, France, Germany, Netherlands and 1 more country. 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 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.
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?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Dec 2020.