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

This study has been terminated.
(voluntary)
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00545948
First received: October 16, 2007
Last updated: February 3, 2011
Last verified: February 2011

October 16, 2007
February 3, 2011
October 2007
January 2013   (final data collection date for primary outcome measure)
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 ]
Two year progression-free survival rate. [ Time Frame: Two year ]
Complete list of historical versions of study NCT00545948 on ClinicalTrials.gov Archive Site
  • 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 ]
Time to progressive disease, which is defined as the time from enrollment to the first date of disease progression.
Not Provided
Not Provided
 
Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer
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 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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Non-Small-Cell Lung
  • 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
  • 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
  • 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.
    Intervention: Drug: Vinorelbine followed by Cisplatin
  • 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.
    Intervention: Drug: Pemetrexed followed by Cisplatin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
117
June 2013
January 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00545948
Pro00000657
Yes
Neal Ready, Ph.D., M.D., Duke University Medical Center, Duke Comprehensive Cancer Center
Duke University
Eli Lilly and Company
Principal Investigator: Neal Ready, Ph.D., M.D. Duke University Medical Center, Hematology/Oncology, Duke Comprehensive Cancer Center
Duke University
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP