Stage IIIA Lung Non-Small Cell Cancer AJCC v7Phase 2NCT01413750
Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer
A Phase 2 study testing Carboplatin, Laboratory Biomarker Analysis and Paclitaxel in people with Stage IIIA Lung Non-Small Cell Cancer AJCC v7 and Stage IIIB Lung Non-Small Cell Cancer AJCC v7, run by National Cancer Institute (NCI) at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7
- What is being tested?
- Carboplatin, Laboratory Biomarker Analysis and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 13 sitesUnited States
- Study dates
- 8 Nov 2010to 14 Apr 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
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.
- Conditions
- Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7
- Being tested
- Carboplatin, Laboratory Biomarker Analysis, Paclitaxel, Placebo Administration, Vorinostat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Placebo AdministrationOther
Given PO
VorinostatDrug
Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (paclitaxel, carboplatin, vorinostat) | Experimental | 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. Receives: Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Drug: Vorinostat |
| Arm II (paclitaxel, carboplatin, placebo) | Active comparator | Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2. Receives: Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Placebo Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year
Secondary outcomes (2)
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.
Measured: 4 weeks from start of treatment, up to 1 year
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.
Measured: 4 weeks from start of treatment, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study start8 Nov 2010
- Primary completion14 Apr 2013
- Study completion14 Apr 2013
Why it stopped: CTEP Initiated Action
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IIIA Lung Non-Small Cell Cancer AJCC v7Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Chandra P Belani, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01413750
- Sponsor's protocol ID
- NCI-2010-02203
- Other IDs
- NCI-2010-02203, PHII-102, 8703, N01CM00038, N01CM00071, N01CM00100, N01CM62209, P30CA033572
- Status last verified
- Oct 2024
- First submitted
- 5 Aug 2011
- Last updated
- 12 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01413750
- Acronym / sponsor ID
- NCI-2010-02203
- Conditions
- Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: CTEP Initiated Action
- Enrolment
- 23 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Nov 2010 (actual)
- Primary completion
- 14 Apr 2013 (actual)
- Study completion
- 14 Apr 2013 (actual)
- First posted
- 10 Aug 2011 (estimated)
- Results
- Posted 18 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (paclitaxel, carboplatin, vorinostat) | Experimental | Drug: Carboplatin, Other: Laboratory Biomarker Analysis, Drug: Paclitaxel, Drug: VorinostatPatients 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 II (paclitaxel, carboplatin, placebo) | Active comparator | Drug: Carboplatin, Other: Laboratory Biomarker Analysis, Drug: Paclitaxel, Other: Placebo AdministrationPatients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Arm I (paclitaxel, carboplatin, vorinostat), Arm II (paclitaxel, carboplatin, placebo) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (paclitaxel, carboplatin, vorinostat), Arm II (paclitaxel, carboplatin, placebo) |
| PaclitaxelAlso: Anzatax, Asotax, Bristaxol, PraxelGiven IV | Drug | Arm I (paclitaxel, carboplatin, vorinostat), Arm II (paclitaxel, carboplatin, placebo) |
| Placebo AdministrationGiven PO | Other | Arm II (paclitaxel, carboplatin, placebo) |
| VorinostatAlso: L-001079038, MSK-390, SAHA, Suberanilohydroxamic AcidGiven PO | Drug | Arm I (paclitaxel, carboplatin, vorinostat) |
Primary outcome
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
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.
2 secondary outcomes
Dose Limiting Toxicity (DLT) (Phase I)
Time frame: 4 weeks from start of treatment, up to 1 year
Maximum Tolerated Dose (MTD) (Phase I)
Time frame: 4 weeks from start of treatment, up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chandra P Belani principal investigator
City of Hope Medical Center
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin, Laboratory Biomarker Analysis and Paclitaxel in people with Stage IIIA Lung Non-Small Cell Cancer AJCC v7 and Stage IIIB Lung Non-Small Cell Cancer AJCC v7, run by National Cancer Institute (NCI) at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.