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Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer

Primary Purpose

Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel
Carboplatin
Vorinostat
Placebo
Laboratory Biomarker Analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IIIA Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically confirmed 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
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy in a metastatic setting
  • 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
  • Patients who have received any prior HDAC inhibitor (except valproic acid for seizure control provided that the valproic acid has been stopped at least 30 days before beginning therapy on this protocol) are excluded from this study
  • 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; patients unable to swallow the vorinostat capsules whole are ineligible (the capsules cannot be crushed or broken)
  • 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; breastfeeding should be discontinued if the mother is treated with vorinostat; women of childbearing potential must use an appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device [IUD], sponge and spermicide, in addition to the male use of a condom) or a prescribed birth control implant or practice abstinence; both double barrier contraception and implants must be used for at least one week prior to the start of the research study and continue for at least two weeks following the last study visit; please note that birth control pills should not be used while on this study as they may have a negative interaction with the experimental drug in this study
  • HIV-positive patients receiving combination antiretroviral therapy are ineligible

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • City of Hope Medical Center
  • USC / Norris Comprehensive Cancer Center
  • University of California Davis Comprehensive Cancer Center
  • Moffitt Cancer Center
  • Emory University/Winship Cancer Institute
  • Illinois CancerCare-Peoria
  • Southern Illinois University School of Medicine - Obstetrics and Oncology
  • Saint John's Mercy Medical Center
  • University of North Carolina
  • Penn State Milton S Hershey Medical Center
  • University of Pittsburgh Cancer Institute
  • University of Pittsburgh
  • Vanderbilt-Ingram Cancer Center
  • Virginia Commonwealth University/Massey Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (paclitaxel, carboplatin, vorinostat)

Arm II (paclitaxel, carboplatin, placebo)

Arm Description

Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.

Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
Estimated using the product-limit method of Kaplan and Meier. PFS defined as time from randomization to progression or death due to any cause. Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

Dose Limiting Toxicity (DLT) (Phase I)
DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count < 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet < 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever > 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD.
Maximum Tolerated Dose (MTD) (Phase I)
The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD.

Full Information

First Posted
August 5, 2011
Last Updated
July 22, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01413750
Brief Title
Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer
Official Title
Phase II Randomized Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Why Stopped
Slow Accrual
Study Start Date
November 2010 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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 is more effective with or without vorinostat in treating non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To compare progression-free survival associated with the combination of carboplatin, paclitaxel and vorinostat versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC. SECONDARY OBJECTIVES: I. To determine the response rate, time to treatment failure, 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 the mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood and archived tumor tissue. An initial safety run-in study is planned (phase I) before starting the phase II randomized study as described below. Doses of Vorinostat to be tested during the safety run-in portion are: Dose Level -1 500 mg QD, Dose Level 1 600 mg QD, Dose Level 2 800 mg QD. Patients will not be randomized during the safety lead-in period, and no patients treated during the lead-in will be considered in the primary evaluation of each arm in any comparison. Once the safety run-in portion is completed, all patients will randomized to receive either placebo or vorinostat at a fixed dose determined during the run-in portion. Phase II Portion of Study: OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat orally (PO) once daily on days -2 to 2. ARM II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2. In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, quarterly for 1 year, and then twice a year thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (paclitaxel, carboplatin, vorinostat)
Arm Type
Experimental
Arm Description
Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat PO once daily on days -2 to 2.
Arm Title
Arm II (paclitaxel, carboplatin, placebo)
Arm Type
Active Comparator
Arm Description
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, TAX
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Estimated using the product-limit method of Kaplan and Meier. PFS defined as time from randomization to progression or death due to any cause. Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year
Secondary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) (Phase I)
Description
DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count < 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet < 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever > 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD.
Time Frame
4 weeks from start of treatment, up to 1 year
Title
Maximum Tolerated Dose (MTD) (Phase I)
Description
The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD.
Time Frame
4 weeks from start of treatment, up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically confirmed 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 Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy in a metastatic setting 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 Patients who have received any prior HDAC inhibitor (except valproic acid for seizure control provided that the valproic acid has been stopped at least 30 days before beginning therapy on this protocol) are excluded from this study 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; patients unable to swallow the vorinostat capsules whole are ineligible (the capsules cannot be crushed or broken) 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; breastfeeding should be discontinued if the mother is treated with vorinostat; women of childbearing potential must use an appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device [IUD], sponge and spermicide, in addition to the male use of a condom) or a prescribed birth control implant or practice abstinence; both double barrier contraception and implants must be used for at least one week prior to the start of the research study and continue for at least two weeks following the last study visit; please note that birth control pills should not be used while on this study as they may have a negative interaction with the experimental drug in this study HIV-positive patients receiving combination antiretroviral therapy are ineligible
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chandra Belani, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Illinois CancerCare-Peoria
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
Southern Illinois University School of Medicine - Obstetrics and Oncology
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62794
Country
United States
Facility Name
Saint John's Mercy Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Penn State Milton S Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer

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