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

This study has been terminated.
(Slow Accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01413750
First received: August 5, 2011
Last updated: July 22, 2015
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Stage IIIA Non-Small Cell Lung Cancer
Stage IIIB Non-Small Cell Lung Cancer
Stage IV Non-Small Cell Lung Cancer
Drug: Paclitaxel
Drug: Carboplatin
Drug: Vorinostat
Other: Placebo
Other: Laboratory Biomarker Analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ 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 ] [ Designated as safety issue: No ]

    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) [ Time Frame: 4 weeks from start of treatment, up to 1 year ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 4 weeks from start of treatment, up to 1 year ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 23
Study Start Date: November 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paclitaxel, carboplatin, vorinostat)
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.
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • TAX
Drug: Carboplatin
Given IV
Drug: Vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
Other: Laboratory Biomarker Analysis
Correlative studies
Active Comparator: Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • TAX
Drug: Carboplatin
Given IV
Other: Placebo
Given PO
Other Name: PLCB
Other: Laboratory Biomarker Analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01413750

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
City of Hope Medical Center
Duarte, California, United States, 91010
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Southern Illinois University School of Medicine - Obstetrics and Oncology
Springfield, Illinois, United States, 62794
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Chandra Belani, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01413750     History of Changes
Other Study ID Numbers: NCI-2010-02203, NCI-2010-02203, PHII-102, 8703, N01CM00100, N01CM00038, U01CA099168, P30CA033572, N01CM00071, N01CM62209
Study First Received: August 5, 2011
Results First Received: June 5, 2015
Last Updated: July 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Paclitaxel
Vorinostat
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on September 02, 2015