Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	California Cancer Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00481078

Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and paclitaxel together with vorinostat is more effective than giving carboplatin and paclitaxel together with a placebo in treating non-small cell lung cancer.

PURPOSE: This randomized phase II trial is studying carboplatin, paclitaxel, and vorinostat to see how well they work compared with carboplatin, paclitaxel, and a placebo in treating patients with stage III or stage IV non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: carboplatin Drug: paclitaxel Drug: placebo Drug: vorinostat	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Paclitaxel Suberoylanilide hydroxamic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind
Official Title:	Randomized Phase II Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to disease progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]
Efficacy [ Designated as safety issue: No ]
Mechanistic aspects of therapy [ Designated as safety issue: No ]

Estimated Enrollment:	93
Study Start Date:	May 2007
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral vorinostat (SAHA) once daily on days 1-14 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV Drug: paclitaxel Given IV Drug: vorinostat Given orally
Arm II: Active Comparator Patients receive an oral placebo once daily on days 1-14 and paclitaxel and carboplatin as in arm l. Treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV Drug: paclitaxel Given IV Drug: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the response rate in patients with stage IIIB or IV non-small cell lung cancer treated with carboplatin, paclitaxel, and vorinostat (SAHA) vs carboplatin, paclitaxel, and placebo.

Secondary

Compare the time to progression and overall survival of patients treated with these regimens.
Compare the safety profiles of these regimens in these patients.
Determine the mechanistic aspects of drug effect via correlative studies on peripheral blood and archived tumor tissue from these patients.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to gender and brain metastasis (present vs absent). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral vorinostat (SAHA) once daily on days 1-14 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3.
Arm II: Patients receive an oral placebo once daily on days 1-14 and paclitaxel and carboplatin as in arm l.

In both arms, treatment repeats every 21 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

Archival tumor tissue blocks are obtained and analyzed for p53, p21, HDAC 6, and ErbB2 expression by immunohistochemistry. Peripheral blood is collected before beginning study treatment and on day 3 of course 1 for analysis of the UGT1A1 polymorphism and proteomic studies. Proteomic profiles are analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry.

After completion of study treatment, patients are followed at 30 days and then every 6-8 weeks for up to 1 year.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed non-small cell lung cancer
- Stage IIIB (with malignant pleural precardial effusion) disease
- Stage IV disease
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
No untreated brain metastases
- Patients with stable brain disease are eligible provided they completed appropriate therapy at least 3 weeks ago (should be off corticosteroids)

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy > 12 weeks
WBC ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Must be able to take oral medications on a continuous basis
No peripheral neuropathy > grade 1
No known history of allergic reactions to paclitaxel
No other uncontrolled illness including, but not limited to, any of the following:
- Active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric or social situations that would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-barrier method contraception for at least 1 week before, during, and for at least 2 weeks after completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior therapy
No prior chemotherapy for advanced or metastatic disease
No prior paclitaxel
At least 3 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
No prior or concurrent valproic acid
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent prophylactic granulocyte growth factors during the first course of study therapy
No other concurrent investigational agents
No other concurrent anticancer agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481078

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
City of Hope Medical Group
Pasadena, California, United States, 91105
Contra Costa Regional Medical Center
Martinez, California, United States, 94553
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 62701
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Evanston Northwestern Healthcare - Evanston Hospital
Evanston, Illinois, United States, 60201-1781
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology-Hematology Associates, Limited at Morris Regional Oncology Center
Morris, Illinois, United States, 60450
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, United States, 61615-7828
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46885-5099
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
Oncology Care Associates, PLLC
Saint Joseph, Michigan, United States, 49085
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Missouri
David C. Pratt Cancer Center at St. John's Mercy
Saint Louis, Missouri, United States, 63141
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

California Cancer Consortium

National Cancer Institute (NCI)

Investigators

Investigator:	Suresh Ramalingam, MD	UPMC Cancer Centers
Study Chair:	Chandra P. Belani, MD	Milton S. Hershey Medical Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000547134, CCC-PHII-82
Study First Received:	May 31, 2007
Last Updated:	October 25, 2008
ClinicalTrials.gov Identifier:	NCT00481078
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Paclitaxel
Lung Neoplasms
Lung Diseases

Vorinostat
Carboplatin
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Protective Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Tubulin Modulators
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 13, 2009