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

This study has been terminated.
Eli Lilly and Company
Information provided by:
Duke University Identifier:
First received: October 16, 2007
Last updated: February 3, 2011
Last verified: February 2011

This study will assign 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). Once patient eligibility is determined, the genomic expression profile will be done on fresh frozen tumor with a diagnosis of non-squamous NSCLC resected at the time of surgery. Two-year progression free survival was chosen as an endpoint in order to assess the effectiveness of directed adjuvant chemotherapy regimens in a population of patients receiving platinum based chemotherapy for early stage non-squamous NSCLC.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Vinorelbine followed by Cisplatin
Drug: Pemetrexed followed by Cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome Measures:
  • Assess if adjuvant chemotherapy using genomic expression profiles to direct sensitivity to vinorelbine or pemetrexed chemotherapy can increase two year disease-free survival rate in completely resected non-squamous NSCLC [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Estimate percentage of completely resected non-squamous NSCLC tumors that can be analyzed and used to direct adjuvant chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Describe overall survival experience of patients treated according to their tumor genomic expression profile for sensitivity to chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assess patient understanding and perceptions of participating in a clinical trial evaluating cancer genomics for adjuvant treatment of early stage lung cancer [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Compare drug sensitivity patterns of cisplatin and pemetrexed in both treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 117
Study Start Date: October 2007
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A-Vinorelbine
Resected tumor will be used for genomic expression profiling. Patients with a genomic expression pattern suggestive of vinorelbine sensitivity will be 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
Arm B-Pemetrexed
Resected tumor will be used for genomic expression profiling. Patients with a genomic expression pattern suggestive of pemetrexed sensitivity will be 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

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 will have no previous treatment for the current diagnosis of non-squamous 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 will be utilized generates a percentage for likelihood of chemotherapy sensitivity. Patients will be 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 cannot be adequately analyzed for gene expression will be offered adjuvant therapy off protocol as deemed appropriate by their primary oncologist.

One hundred and seventeen patients with stage IB (> 4 cm), II or IIIA non-squamous NSCLC will be enrolled. The vinorelbine-sensitive tumors group will receive 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 will receive pemetrexed 500 mg/m2 day 1 followed by cisplatin 75 mg/m2 day 1, every 21 days for 4 cycles. Standard pre-medication regimens will include 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.

A pilot study is appropriate in this case because currently there is not a defined clinical role for genomics technology in determining therapy for NSCLC. The two chemotherapy regimens provided to the study patients are active agents in the treatment of non-squamous NSCLC. Study treatment will consist of 4 cycles of chemotherapy.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Please refer to this study by its identifier: NCT00545948

United States, Florida
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, North Carolina
Presbyterian HealthCare
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Maria Parham Hospital
Henderson, North Carolina, United States, 27536
Scotland HealthCare System (Scotland Memorial Hospital)
Laurinburg, North Carolina, United States, 28352
Southeastern Regional Medical Center, Gibson Cancer Center
Lumberton, North Carolina, United States, 28358
Duke Raleigh Hospital
Raleigh, North Carolina, United States, 27609
Johnston Memorial Hospital Authority
Smithfield, North Carolina, United States, 27577
Columbus County Hospital
Whiteville, North Carolina, United States, 28472
United States, South Carolina
Beaufort Memorial Hospital
Beaufort, South Carolina, United States, 29902
Coastal Cancer Center
Myrtle Beach, South Carolina, United States, 29572
United States, Virginia
Community Memorial Health Center
South Hill, Virginia, United States, 23970
Sponsors and Collaborators
Duke University
Eli Lilly and Company
Principal Investigator: Neal Ready, Ph.D., M.D. Duke University Medical Center, Hematology/Oncology, Duke Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: Neal Ready, Ph.D., M.D., Duke University Medical Center, Duke Comprehensive Cancer Center Identifier: NCT00545948     History of Changes
Other Study ID Numbers: Pro00000657
Study First Received: October 16, 2007
Last Updated: February 3, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Non-Small-Cell Lung Cancer
Guided Therapy
Directed Therapy
Genomic Expression Profiles
Chemotherapy Sensitivity

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic processed this record on April 17, 2014