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

Study Overview
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Brief Summary
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This is a clinical trial to determine the safety and tolerability of MK0683 in combination with gemcitabine and cisplatin and/or carboplatin.

Official Title
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A Phase I Clinical Trial of Vorinostat in Combination With Gemcitabine Plus Platinum in Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: vorinostat
* Drug: Gemcitabine
* Drug: Platinum-based agent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have a histologically-confirmed metastatic or locally advanced non-small cell lung cancer that has not been previously treated with systemic chemotherapy or has received non-platinum and non-gemcitabine based neoadjuvant or adjuvant chemotherapy if the last dose was at least 6 months prior to study enrollment Exclusion Criteria: Patient who has had chemotherapy, radiotherapy, or biological therapy prior to entering the study, except for adjuvant or neoadjuvant chemotherapy, as allowed for treatment of a tumor

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorinostat + Gemcitabine + Platinum-based agent<br> | Drug: vorinostat<br>* Dose escalation study: vorinostat 300-500 mg capsules once daily for 7-14 days in continuous cycles of 21 days<br>Drug: Gemcitabine<br>* Dose escalation study: Gemcitabine 1000-1250 mg/m2 will be given for 2 days in each 21 day cycle<br>Drug: Platinum-based agent<br>* Cisplatin IV 75 mg/m2 will be given for 1 day in each 21 day cycle or carboplatin dosed according to renal function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | every 21 days (every cycle), up to 126 days (6 cycles) | 
| 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. | every 21 days (every cycle), up to 126 days (6 cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | every 21 days (every cycle), up to 126 days (6 cycles) | 
| 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). | every 21 days (every cycle), up to 126 days (6 cycles) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Stage IIIB/IV Non-Small Cell Lung Cancer