Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer (TOP0703)

June 25, 2014 updated by: Duke University

Phase II Prospective Study Evaluating the Role of Directed Cisplatin Based Chemo With Either Vinorelbine or Pemetrexed for the Adj Tx of Early Stage NSCLC in Patients Using Genomic Expression Profiles of Chemo Sensitivity to Guide Therapy

This study assigned subjects to either cisplatin/vinorelbine or cisplatin/pemetrexed chemotherapy using a genomic based expression profile to determine chemotherapy sensitivity in completely resected early stage non-squamous non-small-cell lung cancer (NSCLC). The vinorelbine-sensitive tumors group received Vinorelbine followed by cisplatin, while the pemetrexed-sensitive tumors group received pemetrexed followed by cisplatin. The primary objective of this trial was to determine whether genomic-based adjuvant chemotherapy treatment increased the 2-year progression-free survival rate in completely resected patients with NSCLC compared to historic controls. Secondary objectives included: 1) estimation of the percentage of completely resected NSCLC tumors that can be adequately analyzed and used to direct specific adjuvant chemotherapy; 2) estimation of the proportion of patients who are assigned to treatment with vinorelbine and pemetrexed; 3) evaluation of drug sensitivity patterns of cisplatin and pemetrexed in both treatment arms; 4) description of the overall median survival experience of treated patients; and 5) assessment of patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proposed study is a multi-center open label phase II study of the chemotherapy doublets cisplatin/vinorelbine and cisplatin/pemetrexed as adjuvant therapy in early stage non-squamous NSCLC.

Eligible patients had no previous treatment for the current diagnosis of NSCLC. The two treatment groups of patients will be determined by gene expression profile analysis of each patient's tumor: one group of vinorelbine-sensitive patients and one group of pemetrexed-sensitive patients. The genomic expression profiling that was utilized generated a percentage for likelihood of chemotherapy sensitivity. Patients were directed to receive the chemotherapy regimen for which the percentage of predicted sensitivity is highest. For instance, if the model predicted the likelihood of tumor sensitivity was 46% to vinorelbine and 48% to pemetrexed, then the adjuvant chemotherapy would be directed to cisplatin/pemetrexed. Patients whose tumors could not be adequately analyzed for gene expression were offered adjuvant therapy off protocol as deemed appropriate by their primary oncologist. Patients with either squamous or non-squamous cell histology were eligible to participate in this study as indicated in study protocols dated prior to January 25, 2010. An amendment to the protocol on January 25, 2010 indicated inclusion of only non-squamous histology. However, because of low accrual after January 25, 2010 (5 patients, including 2 screen failures), this report reflects the original study outcomes that includes both squamous and non-squamous histologies.

Thirty-one patients with stage IB (> 4 cm), II or IIIA non-squamous NSCLC were enrolled, from which 24 were assigned treatment. The vinorelbine-sensitive tumors group received Vinorelbine 25 mg/m2 days 1 and 8, followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. The pemetrexed-sensitive tumors group received pemetrexed 500 mg/m2 day 1 followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. Standard pre-medication regimens included dexamethasone, vitamin B12 and folate supplementation in the pemetrexed group. Patients in both groups will receive up to a maximum of 4 cycles of therapy.

Subsequent reevaluation of the genomic signatures of chemotherapy sensitivity have shown that they were irreproducible, suggesting inaccurate patient assignments into the two treatment arms. As a result, it would be inappropriate to separately analyze outcomes for the different treatment groups. Instead, information from both arms will be combined to reflect the overall measure of two-year progression-free survival in this study. Similarly for secondary objectives, both arms will be combined to address endpoints.

To assess patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer, patients provided responses for the following questions at baseline:

  1. Did your doctor talk to you today about choosing chemotherapy treatment for lung cancer based on the genomics of your tumor?
  2. How well did you understand what you doctor told you about choosing chemotherapy based on the genomics of your tumor? (circle a number between 1 and 7, where 1 = very poorly and 7 = very well)
  3. Do you think the type of chemotherapy that you will get is based on the genomics of your tumor?
  4. Do you think you will get better medical care for the treatment of your lung cancer if it is based on the genomics of your tumor?
  5. To what extent do you think treating lung cancer based on the genomics of the tumor will lead to more successful treatment strategies? (circle a number between 1 and 7, where 1 = definitely will not lead to a more successful treatment and 7 = definitely will lead to a more successful treatment)
  6. How effective do you think chemotherapy will be at stopping your cancer from coming back? (circle a number between 1 and 7, where 1 = not at all effective and 7 = completely effective)
  7. To what extent is YOUR lung cancer primarily caused by genetics? (circle a number between 1 and 7, where 1 = not at all caused by genetics and 7 = completely caused by genetics)
  8. To what extent to do you think your lung cancer is treatable? (circle a number between 1 and 7, where 1 = definitely not treatable and 7 = definitely treatable)
  9. Did your doctor talk to you about your chance of your lung cancer coming back? (Yes - go to question 10, No - go to question 11, Do not know - go to question 11)
  10. What did your doctor say was your chance of your cancer coming back? (Low Risk, Moderate or intermediate risk, High risk, Do not know)
  11. What do you think is your chance of your lung cancer coming back in the next year on a scale from 1 to 7 where 1=definitely will not come back and 7=definitely will come back?
  12. How worried are you that your lung cancer will come back in the next year? (circle a number between 1 and 7, where 1=not at all worried and 7=extremely worried)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • West Palm Beach, Florida, United States, 33401
        • Palm Beach Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Presbyterian Healthcare
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Henderson, North Carolina, United States, 27536
        • Maria Parham Hospital
      • Laurinburg, North Carolina, United States, 28352
        • Scotland HealthCare System (Scotland Memorial Hospital)
      • Lumberton, North Carolina, United States, 28358
        • Southeastern Regional Medical Center, Gibson Cancer Center
      • Raleigh, North Carolina, United States, 27609
        • Duke Raleigh Hospital
      • Smithfield, North Carolina, United States, 27577
        • Johnston Memorial Hospital Authority
      • Whiteville, North Carolina, United States, 28472
        • Columbus County Hospital
    • South Carolina
      • Beaufort, South Carolina, United States, 29902
        • Beaufort Memorial Hospital
      • Myrtle Beach, South Carolina, United States, 29572
        • Coastal Cancer Center
    • Virginia
      • South Hill, Virginia, United States, 23970
        • Community Memorial Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients are eligible to be included in the study only if they meet all of the following criteria:

  1. Patients with completely resected stage IB (> 4 cm), II, or IIIA Non-Squamous NSCLC. Patient must be enrolled and begin therapy within 4 to 12 weeks from the date of complete surgical resection.
  2. Fresh tissue must be available for genomics expression profiling.
  3. ECOG performance status of 0 or 1.
  4. NO prior chemotherapy, radiation therapy, or biologic/targeted therapy within the last 5 years. Prior therapy with low dose methotrexate or similar medications is allowed if therapy used to treat non-malignant conditions.
  5. Age ≥ 18 years.
  6. No previous or concomitant malignancy in the past 5 years other than curatively-treated carcinoma in situ of the cervix, or basal cell or squamous cell carcinoma of the skin.
  7. No other serious medical or psychiatric illness.
  8. Signed informed consent.

  9. Required laboratory data within one week of enrollment:

    • ANC or AGC ≥ 1500 per uL;
    • Platelets ≥ 100,000 per uL;
    • Total bilirubin ≤ 1.5 mg/dL;
    • Creatinine ≤ 2 mg/dL; creatinine clearance ≥ 45 mL/min;
    • SGOT/SGPT ≤ 1.5x ULN.
  10. Females of child-bearing potential (not surgically sterilized and between menarche and 1 year post menopause) must test negative for pregnancy within 7 days prior to or at the time of enrollment based on a serum pregnancy test. Both sexually active males and females of reproductive potential must agree to use a reliable method of birth control, as determined by the patient and their health care team, during the study and for 3 months following the last dose of study drug.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

  1. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
  2. Concurrent administration of any other anti-tumor therapy (see #4 inclusion for exceptions).
  3. Inability to comply with protocol or study procedures.
  4. Active infection requiring IV antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  5. Major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant systemic disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
  6. Myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications.
  7. Contraindication to corticosteroids.
  8. Inability or unwillingness to take folic acid or vitamin B12 supplementation.
  9. Unwillingness to stop taking herbal supplements while on study.
  10. Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry and throughout study enrollment as the distribution of pemetrexed in this fluid space is not fully understood.
  11. Inability to discontinue administration of aspirin at a dose > 1300 mg/day or other long acting, non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam). Moderate dose ibuprofen may be continued.
  12. Female patients that are pregnant or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Arm A-Vinorelbine
Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of vinorelbine sensitivity were given cisplatin + vinorelbine.
Drug: Vinorelbine followed by Cisplatin
Vinorelbine 25 mg/m2 IV over 6-10 minutes on days 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes on day 1 (every 21 days x 4 cycles).
Other Names:
  • Navelbine
  • Platinol
Other: Arm B-Pemetrexed
Resected tumor was used for genomic expression profiling. Patients with a genomic expression pattern suggestive of pemetrexed sensitivity were given cisplatin + pemetrexed.
Drug: Pemetrexed followed by Cisplatin
Pemetrexed 500 mg/m2 IV infusion over approximately 10 minutes on day 1, followed by Cisplatin 75 mg/m2 IV over 60 min on day 1 (every 21 days x 4 cycles)
Other Names:
  • Alimta
  • Platinol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
2-Year Progression-Free Survival Rate in Patients With Completely Resected Stage IB, II, or IIIA NSCLC
Time Frame: 2 years
Progression-free survival time was defined as the time from initiation of study treatment to the first date of disease progression or death as a result of any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Time was censored at the date of the last follow-up visit for patients who were still alive and have not progressed. The two-year progression free survival rate is a percentage, representing the fraction of treated patients who, after two years, are disease free or alive.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Completely Resected NSCLC Tumors That Can Be Analyzed and Used to Direct Adjuvant Chemotherapy
Time Frame: 4 years
The percentage of patients with completely resected NSCLC tumors who had successful genomic analysis and assigned to treatment among patients. All 31 patients enrolled in the study had completely resected tumors. These tumors included a mixture of squamous and non-squamous histologies as indicated the original protocol. However, an amendment dated January 25, 2010 limited eligibility to patients with non-squamous disease. Given that only 5 patients were accrued into the study after this amendment, results reported will consider all histologies.
4 years
2-Year Overall Survival in Patients Treated for NSCLC
Time Frame: 2 years
Overall survival time was defined as the time from initiation of study treatment to the date of death as a result of any cause. Time was censored at the date of the last follow-up visit for patients who were still alive. The two-year overall survival rate is a percentage, representing the fraction of treated patients who, after two years, are alive
2 years
Patient Understanding and Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for Adjuvant Treatment of Early Stage Lung Cancer
Time Frame: Baseline
Do to space limitations, see the Detailed Description in the study protocol for the wording of the questions used in the Patient Expectations Questionnaire.
Baseline
Compare Drug Sensitivity Patterns of Cisplatin and Pemetrexed in Both Treatment Arms
Time Frame: 2 years
Using genomics-based prediction models previously developed separately for cisplatin and pemetrexed, the probability that each patient was sensitive or would respond to treatment was computed. Quartiles describe the patterns of drug sensitivity probabilities. The 1st, 2nd, and 3rd quartiles are the sensitivity levels at which 25%, 50%, and 75% of patients have lower sensitivity. There is lack of integrity regarding the available data due to irreproducible genomic signatures. Therefore the results of this outcome are not presented.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Duke University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eli Lilly and Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Neal Ready, Ph.D., M.D., Duke University Medical Center, Hematology/Oncology, Duke Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 16, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 21, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00000657

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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