Advanced Solid Tumors, Excluding Breast CancerPhase 1CTKI258A2120NCT01700270
Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors.
A Phase 1 study testing dovitinib (TKI258) and fluvoxamine in people with Advanced Solid Tumors, Excluding Breast Cancer, run by Novartis Pharmaceuticals at 6 sites in 4 countries.
Trial summary
This is a multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI) study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in patients with advanced solid tumors, excluding breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Excluding Breast Cancer
- What is being tested?
- dovitinib (TKI258) and fluvoxamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 6 sitesin 4 countries
- Study dates
- May 2013to Aug 2014
- 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
- Patients with a cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor, excluding breast cancer which has progressed despite standard therapy or for which no standard therapy exists - ECOG performance status 0 or 1 and an anticipated life expectancy of ≥3 months- Patient must meet protocol-specific laboratory values
Who cannot join
- Patients with brain metastases - Patients who have received or who are expected to receive any prohibited medications and therapies - Patients who have received CYP1A2 or CYP3A inhibitor medications within 5 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who have received CYP1A2 or CYP3A inducer medications within 30 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who are actively taking antidepressants, benzodiazepines, serotonergic drugs, and/or monoamine oxidase inhibitors (MAOIs) - Patients who have not recovered from previous anti-cancer therapies - Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258 - Patients who have concurrent severe and/or uncontrolled concomitant medical conditions that could compromise participation in the study - Female patients who are pregnant or breast-feeding - Fertile males or women not willing to use highly effective methods of contraception - Other protocol-defined inclusion/exclusion criteria will apply
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States2 sites
Cancer Therapy & Research Center / UT Health Science Center SC
San Antonio, Texas, 78229
Montefiore Medical Center Montefiore Medical Center (SC)
The Bronx, New York, 10467
Switzerland2 sites
Novartis Investigative Site
Chur, 7000
Novartis Investigative Site
Geneva, 1211
About this study
Official title: A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of the CYP1A2 Inhibitor, Fluvoxamine, on Dovitinib (TKI258) Pharmacokinetics in Patients With Advanced Solid Tumors
This is a multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI) study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in patients with advanced solid tumors, excluding breast cancer. The purpose of this study is to evaluate the effect of a CYP1A2 inhibitor, 100 mg fluvoxamine, on the PK of dovitinib when administered at a dose of 300 mg on the dosing schedule, 5 days on/2 days off. The study will consist of 2 phases: a Pharmacokinetic (PK) phase and a clinical treatment phase. The DDI test will be conducted in the PK phase. The DDI test will assess the steady state PK profile of dovitinib when administered alone and in the presence of the CYP1A2 inhibitor, fluvoxamine (AUC 0-24h, AUC 0-72h and Cmax parameters). During the clinical treatment phase patients may continue to receive treatment with TKI258 until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
- Being tested
- dovitinib (TKI258), fluvoxamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dovitinib (TKI258)Drug
fluvoxamineDrug
perpetrator drug; 7 days of dosing
| Study group | Role | What they receive |
|---|---|---|
| dovitinib (TKI258) | Experimental | dovitinib, 5 days on / 2 days off dose schedule Receives: Drug: dovitinib (TKI258); Drug: fluvoxamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)
Measured: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
Secondary outcomes (3)
Frequency and severity of AEs (Adverse Events)
Measured: up to at least 30 days after the last dose of dovitinib (TKI258)
Frequency and severity of SAEs (Serious Adverse Events)
Measured: up to at least 30 days after the last dose of dovitinib (TKI258)
Preliminary evidence of antitumor activity of dovitinib (TKI258)
overall response based on investigator assessment and best overall response using RECIST 1.1
Measured: every 8 weeks until progression of disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startMay 2013
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumors, Excluding Breast 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 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
- NCT01700270
- Sponsor's protocol ID
- CTKI258A2120
- Other IDs
- 2012-001546-18
- Acronym
- CTKI258A2120
- Status last verified
- Nov 2014
- First submitted
- 2 Oct 2012
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
de Weger VA, Goel S, von Moos R, Schellens JHM, Mach N, Tan E, Anand S, Scott JW, Lassen U. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Jan;81(1):73-80. doi: 10.1007/s00280-017-3469-4. Epub 2017 Nov 3.
PubMed 29101463
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, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of the CYP1A2 Inhibitor, Fluvoxamine, on Dovitinib (TKI258) Pharmacokinetics in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01700270
- Acronym / sponsor ID
- CTKI258A2120 / CTKI258A2120
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 4 Oct 2012 (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 multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI) study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in patients with advanced solid tumors, excluding breast cancer. The purpose of this study is to evaluate the effect of a CYP1A2 inhibitor, 100 mg fluvoxamine, on the PK of dovitinib when administered at a dose of 300 mg on the dosing schedule, 5 days on/2 days off. The study will consist of 2 phases: a Pharmacokinetic (PK) phase and a clinical treatment phase. The DDI test will be conducted in the PK phase. The DDI test will assess the steady state PK profile of dovitinib when administered alone and in the presence of the CYP1A2 inhibitor, fluvoxamine (AUC 0-24h, AUC 0-72h and Cmax parameters). During the clinical treatment phase patients may continue to receive treatment with TKI258 until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dovitinib (TKI258) | Experimental | Drug: dovitinib (TKI258), Drug: fluvoxaminedovitinib, 5 days on / 2 days off dose schedule |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with a cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor, excluding breast cancer which has progressed despite standard therapy or for which no standard therapy exists - ECOG performance status 0 or 1 and an anticipated life expectancy of ≥3 months- Patient must meet protocol-specific laboratory values
Key exclusion criteria (1 listed)
- Patients with brain metastases - Patients who have received or who are expected to receive any prohibited medications and therapies - Patients who have received CYP1A2 or CYP3A inhibitor medications within 5 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who have received CYP1A2 or CYP3A inducer medications within 30 days prior to start study treatment or are expected to receive during the first 28 days after starting the study treatment - Patients who are actively taking antidepressants, benzodiazepines, serotonergic drugs, and/or monoamine oxidase inhibitors (MAOIs) - Patients who have not recovered from previous anti-cancer therapies - Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258 - Patients who have concurrent severe and/or uncontrolled concomitant medical conditions that could compromise participation in the study - Female patients who are pregnant or breast-feeding - Fertile males or women not willing to use highly effective methods of contraception - Other protocol-defined inclusion/exclusion criteria will apply
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 |
|---|---|---|
| dovitinib (TKI258) | Drug | dovitinib (TKI258) |
| fluvoxamineperpetrator drug; 7 days of dosing | Drug | dovitinib (TKI258) |
Primary outcome
TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)
Time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
3 secondary outcomes
Frequency and severity of AEs (Adverse Events)
Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
Frequency and severity of SAEs (Serious Adverse Events)
Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
Preliminary evidence of antitumor activity of dovitinib (TKI258)
Time frame: every 8 weeks until progression of disease
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.
- Derived from this study: PubMed 29101463de Weger VA, Goel S, von Moos R, Schellens JHM, Mach N, Tan E, Anand S, Scott JW, Lassen U. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2018 Jan;81(1):73-80. doi: 10.1007/s00280-017-3469-4. Epub 2017 Nov 3.
- Results for CTKI258A2120 on the Novartis Clinical Trial 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
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dovitinib (TKI258) and fluvoxamine in people with Advanced Solid Tumors, Excluding Breast Cancer, run by Novartis Pharmaceuticals at 6 sites in 4 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 1 inclusion and 1 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 6 sites in United States, Switzerland, Denmark, Netherlands. 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?
TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug) (time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)). The study lists 7 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 NCT01700270, which also lists 1 linked publication.
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.