A Study of Vorinostat in Patients With Solid Tumors (MK-0683-029)
- Registration Number
- NCT00127127
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The primary purpose of this trial is to determine the maximum tolerated dose (MTD), or the maximum acceptable dose (MAD) and evaluate the dose limiting toxicity (DLT) of oral suberoylanilide hydroxamic acid in participants with solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- Participants with histologically or cytologically diagnosed solid tumor; no standard therapy available or participant has failed to respond to standard therapy
- Participants with history of immunotherapy, radiotherapy, surgery, or chemotherapy during the previous 4 weeks; previous treatment is 5 or more chemotherapeutic regimens.
- Any uncontrolled concomitant illness
- Are pregnant or breast-feeding
- Serious drug or food allergy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Vorinostat 500 mg vorinostat During Cycle 1, participants receive a single oral dose of vorinostat 500 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive a single oral dose of vorinostat 500 mg once-daily in the morning. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy on the Cycle 2 and subsequent cycles.(Each cycle will be 26 days.) Vorinostat 100 mg vorinostat During Cycle 1, participants receive a single oral dose of vorinostat 100 mg on Day 1 in a fasted state, Day 3 in a fed state, and Day 19 in a fed state. On Days 5-18, participants receive vorinostat 100 mg twice daily, in the morning and evening. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.) Vorinostat 200 mg vorinostat During Cycle 1, participants receive a single oral dose of vorinostat 200 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive vorinostat 200 mg twice daily, in the morning and evening. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.) Vorinostat 400 mg vorinostat During Cycle 1, participants receive a single oral dose of vorinostat 400 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive a single oral dose of vorinostat 400 mg once-daily in the morning. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.)
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced One or More Adverse Events Up to approximately 4 years An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event Up to approximately 4 years An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 Up to 26 days A DLT was defined as an event considered to be related to study treatment and included: 1) Grade 4 neutropenia refractory to treatments persisting more than 5 days; 2) Grade 3 or more severe neutropenic fever; 3) Grade 3 thrombocytopenia requiring blood transfusions or Grade 4 thrombocytopenia; 4) Grade 4 hemoglobin decrease; 5) Grade 3 or more severe non-hematological toxicities other than anorexia, nausea/vomiting, and fatigue. (For the diarrhea, it was defined as not to use the frequency for the grading. For the alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]), it was defined as the case of over 300 IU/L; 6) Grade 3 or more severe anorexia, nausea/vomiting, and fatigue refractory to treatments; and 7) compliance of the study drug, while administrating 14 consecutive days, was less than 50% due to the drug-related adverse experience.
- Secondary Outcome Measures
Name Time Method AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State Day 1: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Cmax of Vorinostat After a Single Oral Dose in a Fed State Day 3: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Tmax of Vorinostat After a Single Oral Dose in a Fed State Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.
t½ of Vorinostat After a Single Oral Dose in a Fed State Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.
t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.