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

NCT00481078 | Completed Phase 2 Results

• 5 other identifiers: NCI-2012-02841PHII-82N01CM62208N01CM62209N01CM62201
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Progression-free Survival

  Up to 1 year

• Overall Survival

  Up to 1 year

Study Arms (2)

Arm I (vorinostat, paclitaxel, carboplatin)

EXPERIMENTAL

Patients receive oral vorinostat (SAHA) at 400 mg once daily on days 1-14 and paclitaxel IV 200 mg/m2 over 3 hours and carboplatin IV dosed to achieve an area under the concentration versus time curve of 6 mg/mLXmin over 30 minutes on day 3.

Drug: vorinostat; Drug: paclitaxel; Drug: carboplatin; Other: laboratory biomarker analysis

Arm II (placebo, paclitaxel, carboplatin)

ACTIVE COMPARATOR

Patients receive an oral placebo once daily on days 1-14 and paclitaxel and carboplatin as in arm l.

Drug: paclitaxel; Drug: carboplatin; Other: placebo; Other: laboratory biomarker analysis

Interventions

vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I (vorinostat, paclitaxel, carboplatin)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Arm I (vorinostat, paclitaxel, carboplatin); Arm II (placebo, paclitaxel, carboplatin)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Arm I (vorinostat, paclitaxel, carboplatin); Arm II (placebo, paclitaxel, carboplatin)

placebo OTHER

Given PO

Also known as: PLCB

Arm II (placebo, paclitaxel, carboplatin)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (vorinostat, paclitaxel, carboplatin); Arm II (placebo, paclitaxel, carboplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vorinostat; Paclitaxel; Taxes; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Coordination Complexes

Results Point of Contact

• Title: DCC Project Administrator
• Organization: California Cancer Consortium

CCCP@coh.org

626-256-4673

Study Officials

• Chandra Belani

  Penn State Hershey Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2007
• First Posted: June 1, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: October 30, 2014
• Results First Posted: October 30, 2014

Record last verified: 2012-12

Locations

US (1)