Advanced Solid Tumors, Excluding Breast CancerPhase 1NCT01596647
Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors
A Phase 1 study testing caffeine, diclofenac and omeprazole in people with Advanced Solid Tumors, Excluding Breast Cancer, run by Novartis Pharmaceuticals at 5 sites in United States.
Trial summary
This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam 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?
- caffeine, diclofenac and omeprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 5 sitesUnited States
- Study dates
- May 2012to Jul 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 anticipated life expectancy ≥ 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 inducer, CYP2C9/2C19 inducer or CYP3A4 inducer medications within 30 days prior to start study treatment or are expected to receive during the first 14 days after starting the study treatment
- Patients with a known hypersensitivity to benzodiazepines
- 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
Show all 10Show fewer
- 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
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Henry Ford Hospital Henry Ford
Detroit, Michigan, 48202-2689
University of Kansas Cancer Center Medical Center
Kansas City, Kansas, 66160
Comprehensive Cancer Centers
Las Vegas, Nevada, 89169
University of Minnesota
Minneapolis, Minnesota, 55455
Cancer Institute of New Jersey Dept of Cancer Institute of NJ
New Brunswick, New Jersey, 08901
About this study
Official title: A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer
This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (TKI258) until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
- Being tested
- caffeine, diclofenac, omeprazole, midazolam, TKI258
- Keywords
- cancer, tumors, phase I, drug-drug interaction, pharmacokinetic, probe drug, caffeine, diclofenac, omeprazole, midazolam, CYP1A2, CYP2C9, CYP2C19, CYP3A4
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
caffeineDrug
Also called probe drug
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
diclofenacDrug
Also called probe drug
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
omeprazoleDrug
Also called probe drug
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
midazolamDrug
Also called probe drug
single dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam
TKI258Drug
Also called dovitinib
dovitinib, 5 days on / 2 days off dose schedule
| Study group | Role | What they receive |
|---|---|---|
| TKI258 (dovitinib) | Experimental | dovitinib, 5 days on / 2 days off dose schedule Receives: Drug: caffeine; Drug: diclofenac; Drug: omeprazole; Drug: midazolam; Drug: TKI258 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCtlast (Area Under the Curve)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCinf
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Tmax (Time to maximum concentration)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: HL (Half-life time)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:CL/F (Apparent Oral Clearance)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Vz/F (apparent volume of distribution)
Measured: multiple time-points over 24h post dose on day 1 and Day 13 (DDI 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)
Preliminary evidence of antitumor activity of dovitinib (TKI258)
overall response based on investigator's assessment and best overall response using RECIST 1.1
Measured: every 8 weeks until progression of disease
Frequency and severity of SAEs (Serious Adverse Events)
Measured: up to at least 30 days after the last dose of dovitinib (TKI258)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2012 (estimated)
- Study startMay 2012
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 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
- NCT01596647
- Sponsor's protocol ID
- CTKI258A2119
- Other IDs
- 2011-001489-16
- Status last verified
- May 2015
- First submitted
- 23 Mar 2012
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- 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, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer
- ClinicalTrials.gov ID
- NCT01596647
- Acronym / sponsor ID
- CTKI258A2119
- Keywords
- cancer, tumors, phase I, drug-drug interaction, pharmacokinetic, probe drug, caffeine, diclofenac, omeprazole, midazolam, CYP1A2, CYP2C9, CYP2C19, CYP3A4
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 11 May 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, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TKI258 (dovitinib) | Experimental | Drug: caffeine, Drug: diclofenac, Drug: omeprazole, Drug: midazolam, Drug: TKI258dovitinib, 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 (3 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 anticipated life expectancy ≥ 3 months
- Patient must meet protocol-specific laboratory values
Key exclusion criteria (10 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 inducer, CYP2C9/2C19 inducer or CYP3A4 inducer medications within 30 days prior to start study treatment or are expected to receive during the first 14 days after starting the study treatment
- Patients with a known hypersensitivity to benzodiazepines
- Patients who have not recovered from previous anti-cancer therapies
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 |
|---|---|---|
| caffeineAlso: probe drugsingle dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam | Drug | TKI258 (dovitinib) |
| diclofenacAlso: probe drugsingle dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam | Drug | TKI258 (dovitinib) |
| omeprazoleAlso: probe drugsingle dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam | Drug | TKI258 (dovitinib) |
| midazolamAlso: probe drugsingle dose of the probe drug cocktail contains: caffeine, diclofenac, omeprazole and midazolam | Drug | TKI258 (dovitinib) |
| TKI258Also: dovitinibdovitinib, 5 days on / 2 days off dose schedule | Drug | TKI258 (dovitinib) |
Primary outcome
Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCtlast (Area Under the Curve)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: AUCinf
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Tmax (Time to maximum concentration)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters: HL (Half-life time)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:CL/F (Apparent Oral Clearance)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI phase),
Probe substrate PK parameters:Vz/F (apparent volume of distribution)
Time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI 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)
Preliminary evidence of antitumor activity of dovitinib (TKI258)
Time frame: every 8 weeks until progression of disease
Frequency and severity of SAEs (Serious Adverse Events)
Time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
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 CTKI258A2119 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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing caffeine, diclofenac and omeprazole in people with Advanced Solid Tumors, Excluding Breast Cancer, run by Novartis Pharmaceuticals at 5 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 3 inclusion and 10 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 5 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 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?
Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug) (time frame: multiple time-points over 24h post dose on day 1 and Day 13 (DDI 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?
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.