A Study of Vorinostat in Patients With Solid Tumors (MK-0683-029)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Clinical Study of L-001079038 in Patients With Solid Tumors

Conditions
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Tumors

Intervention / Treatment
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* Drug: vorinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with histologically or cytologically diagnosed solid tumor; no standard therapy available or participant has failed to respond to standard therapy Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorinostat 100 mg<br>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.) | Drug: vorinostat<br>* vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration<br>* Other names: suberoylanilide hydroxamic acid (SAHA);|
| Experimental: Vorinostat 200 mg<br>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.) | Drug: vorinostat<br>* vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration<br>* Other names: suberoylanilide hydroxamic acid (SAHA);|
| Experimental: Vorinostat 400 mg<br>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.) | Drug: vorinostat<br>* vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration<br>* Other names: suberoylanilide hydroxamic acid (SAHA);|
| Experimental: Vorinostat 500 mg<br>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.) | Drug: vorinostat<br>* vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration<br>* Other names: suberoylanilide hydroxamic acid (SAHA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced One or More Adverse Events | 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. | Up to approximately 4 years | 
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 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. | Up to approximately 4 years | 
| Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | 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. | Up to 26 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. | 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 of Vorinostat After a Single Oral Dose in a Fed State | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. | 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 of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. | Day 1: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Cmax of Vorinostat After a Single Oral Dose in a Fed State | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. | Day 3: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. | Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Tmax of Vorinostat After a Single Oral Dose in a Fed State | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. | Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | 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. | Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| t½ of Vorinostat After a Single Oral Dose in a Fed State | 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. | Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 
| t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 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. | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors