Vorinostat, Carboplatin, and Paclitaxel in Treating Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00481078
• Other study ID #: NCI-2012-02841
• Secondary ID: PHII-82N01CM6220
• Status: Completed
• Phase: Phase 2
• First received: May 31, 2007
• Last updated: October 24, 2014
• Start date: May 2007
• Est. completion date: July 2009

Study information

• Verified date: December 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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. 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

Description:

PRIMARY OBJECTIVES:

I. To compare the response rate associated with the combination of vorinostat, carboplatin, paclitaxel versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC.

SECONDARY OBJECTIVES:

I. To determine the time to progression and overall survival for the two regimens.

II. To assess the safety profile of the regimen of vorinostat, carboplatin and paclitaxel for patients with advanced NSCLC.

III. To understand mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood, archived tumor tissue, and paired biopsies in consenting 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically confirmed stage IIIB (with malignant pleural pericardial effusion) or stage IV non-small cell lung cancer

• No prior chemotherapy for advanced or metastatic disease

• ECOG performance status 0 or 1

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• Life expectancy of greater than 12 weeks

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Vorinostat can cause fetal harm when administered to a pregnant woman; there are no adequate and well-controlled studies in pregnant women; if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not be receiving any other investigational agents

• Patients with untreated brain metastases should be excluded from this clinical trial; however, patients who have stable brain disease (should be off corticosteroids) at least 3 weeks after completion of appropriate therapy are eligible

• Prior or current use of valproic acid, a HDAC inhibitor

• Peripheral neuropathy of severity greater than grade 1

• Known history of allergic reactions to paclitaxel

• Prior therapy with paclitaxel

• Inability to take oral medications on a continuous basis

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because vorinostat is an HDAC inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat; these potential risks may also apply to other agents used in this study

• HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-small Cell Lung Cancer
• Stage IIIB Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• vorinostat
Given PO
• paclitaxel
Given IV
• carboplatin
Given IV

Other:
• placebo
Given PO
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate	Each patient will be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, insufficient data).; Patients with confirmed CR or PR according to the RECIST criteria were considered to have responded to treatment.	Assessed every two cycles	No
Secondary	Progression-free Survival	Evaluated using the Kaplan-Meier method. Compared between arms using the log-rank test.	Up to 1 year	No
Secondary	Overall Survival	Evaluated using the Kaplan-Meier method. Compared between arms using the log-rank test.	Up to 1 year	No