A Phase I Clinical Study of L-001079038 in Patients With Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- vorinostat
- Conditions
- Tumors
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 18
- Primary Endpoint
- Number of Participants Who Experienced One or More Adverse Events
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Vorinostat 100 mg
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.)
Intervention: vorinostat
Vorinostat 200 mg
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.)
Intervention: vorinostat
Vorinostat 400 mg
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.)
Intervention: vorinostat
Vorinostat 500 mg
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.)
Intervention: vorinostat
Outcomes
Primary Outcomes
Number of Participants Who Experienced One or More Adverse Events
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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 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)
- 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 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 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)
- 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 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 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)
- 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 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 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)