Clinical Trial of MK0683 in Combination With FDA Approved Cancer Drugs in Patients With Advanced NSCLC (MK0683-058)

실험적: Vorinostat + Gemcitabine + Platinum-based agent

의약품: vorinostat

Dose escalation study: vorinostat 300-500 mg capsules once daily for 7-14 days in continuous cycles of 21 days

의약품: Gemcitabine

Dose escalation study: Gemcitabine 1000-1250 mg/m2 will be given for 2 days in each 21 day cycle

의약품: Platinum-based agent

Cisplatin IV 75 mg/m2 will be given for 1 day in each 21 day cycle or carboplatin dosed according to renal function.

Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin

DLT = any Common Terminology Criteria for Adverse Events Grade 3/4 drug related non-hematologic toxicity EXCEPT Grade 3 nausea/vomiting responsive to therapy, Grade 3 Fatigue responsive to management, transient electrolyte disorders that were corrected, any Grade 4 drug related hematologic toxicity EXCEPT lymphopenia/neutropenia, unless the neutropenia was febrile and/or was an infection requiring treatment, OR Any Grade 4 neutropenia lasting >=7 days, failure of absolute neutrophil count or platelets to recover, or any drug-related AE that led to a dose reduction of >=1 study drugs.

Maximum Tolerated Dose of Vorinostat Administered in Combination With Standard Doses of Gemcitabine Plus Either Cisplatin or Carboplatin in Patients With Advanced Stage Non-Small Cell Lung Cancer Who Have Not Received Chemotherapy for Advanced Disease

Maximum tolerated dose (MTD) was defined as the highest dose level in which fewer than 2 patients among the first 6 enrolled experience a DLT (as defined in Outcome Measure 1) during the first cycle of treatment.

The MTD was 400 mg for up to 10 days in 21-day cycles.

Number of Participants With Clinical Adverse Experiences (Safety and Tolerability)

An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.

The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively).

Number of Participants With Laboratory Adverse Experiences (Safety and Tolerability)

An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.

The AEs could have been any grade from 1 to 5 in severity (mild, moderate, severe, life-threatening, death, respectively).