Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors. (CTKI258A2120)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 400 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Solid Tumors, Excluding Breast Cancer |
Drug: dovitinib (TKI258) Other: fluvoxamine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- Frequency and severity of AEs (Adverse Events) [ Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258) ] [ Designated as safety issue: Yes ]
- Frequency and severity of SAEs (Serious Adverse Events) [ Time Frame: up to at least 30 days after the last dose of dovitinib (TKI258) ] [ Designated as safety issue: Yes ]
- Preliminary evidence of antitumor activity of dovitinib (TKI258) [ Time Frame: every 8 weeks until progression of disease ] [ Designated as safety issue: No ]overall response based on investigator assessment and best overall response using RECIST 1.1
| Estimated Enrollment: | 32 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | April 2014 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: dovitinib (TKI258)
dovitinib, 5 days on / 2 days off dose schedule
|
Drug: dovitinib (TKI258)
Other: fluvoxamine
single dose - perpetrator drug
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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, 1 or 2 - Patient must meet protocol-specific laboratory values
Exclusion Criteria:
- 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
Contacts and Locations| Contact: Novartis Pharmaceuticals | +1(800)340-6843 |
| United States, Missouri | |
| Washington University School Of Medicine-Siteman Cancer Ctr Wash Univ | Not yet recruiting |
| St. Louis, Missouri, United States, 63110 | |
| Contact: Lauren Trull 314-747-5372 trulll@siteman.wustl.edu | |
| Principal Investigator: Craig Lockhart | |
| United States, New York | |
| Montefiore Medical Center Montefiore Medical Center (SC) | Not yet recruiting |
| Bronx, New York, United States, 10467 | |
| Contact: Christina Garcia-Miller 718-405-8515 crgarcia@montefiore.org | |
| Principal Investigator: Sanjay Goel | |
| United States, Texas | |
| Cancer Therapy & Research Center / UT Health Science Center SC | Not yet recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Ellen Jones 210-450-5976 regulatoryaffairs@uthscsa.edu | |
| Principal Investigator: John Sarantopoulos | |
| Denmark | |
| Novartis Investigative Site | Not yet recruiting |
| Copenhagen, Denmark, DK-2100 | |
| Netherlands | |
| Novartis Investigative Site | Not yet recruiting |
| Amsterdam, Netherlands, 1066 CX | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01700270 History of Changes |
| Other Study ID Numbers: | CTKI258A2120, 2012-001546-18 |
| Study First Received: | October 2, 2012 |
| Last Updated: | May 10, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Fluvoxamine Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Central Nervous System Agents Therapeutic Uses Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants |
ClinicalTrials.gov processed this record on May 23, 2013