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

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00423449

Purpose

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

Condition	Intervention	Phase
Non-Small Cell Lung Cancer	Drug: vorinostat Drug: Gemcitabine Drug: Platinum-based agent	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Clinical Trial of Vorinostat in Combination With Gemcitabine Plus Platinum in Patients With Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Number of Participants With Dose-limiting Toxicities (DLT) Due to Vorinostat Administered in Combination With Standard Dose of Gemcitabine Plus Either Cisplatin or Carboplatin [ Time Frame: every 21 days (every cycle), up to 126 days (6 cycles) ] [ Designated as safety issue: Yes ]
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 [ Time Frame: every 21 days (every cycle), up to 126 days (6 cycles) ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Number of Participants With Clinical Adverse Experiences (Safety and Tolerability) [ Time Frame: every 21 days (every cycle), up to 126 days (6 cycles) ] [ Designated as safety issue: Yes ]
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) [ Time Frame: every 21 days (every cycle), up to 126 days (6 cycles) ] [ Designated as safety issue: Yes ]
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).

Enrollment:	61
Study Start Date:	March 2007
Study Completion Date:	April 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Vorinostat + Gemcitabine + Platinum-based agent	Drug: vorinostat Dose escalation study: vorinostat 300-500 mg capsules once daily for 7-14 days in continuous cycles of 21 days Drug: Gemcitabine Dose escalation study: Gemcitabine 1000-1250 mg/m2 will be given for 2 days in each 21 day cycle Drug: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00423449

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00423449 History of Changes
Other Study ID Numbers:	MK-0683-058, 2006_528
Study First Received:	January 17, 2007
Results First Received:	July 6, 2011
Last Updated:	July 6, 2011
Health Authority:	France: Ministry of Health

Keywords provided by Merck:

Advanced Stage IIIB/IV Non-Small Cell Lung Cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Vorinostat
Antimetabolites, Antineoplastic

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012