Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
(Study terminated due to reproducibility issues with genomics prediction model.)
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00545948
First received: October 16, 2007
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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.


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:
  • 2-Year Progression-Free Survival Rate in Patients With Completely Resected Stage IB, II, or IIIA NSCLC [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Patients With Completely Resected NSCLC Tumors That Can Be Analyzed and Used to Direct Adjuvant Chemotherapy [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.

  • 2-Year Overall Survival in Patients Treated for NSCLC [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Patient Understanding and Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for Adjuvant Treatment of Early Stage Lung Cancer [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Do to space limitations, see the Detailed Description in the study protocol for the wording of the questions used in the Patient Expectations Questionnaire.

  • Compare Drug Sensitivity Patterns of Cisplatin and Pemetrexed in Both Treatment Arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: December 2007
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

  Show Detailed Description

  Eligibility

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

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
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: NCT00545948

Locations
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
Investigators
Principal Investigator: Neal Ready, Ph.D., M.D. Duke University Medical Center, Hematology/Oncology, Duke Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00545948     History of Changes
Other Study ID Numbers: Pro00000657
Study First Received: October 16, 2007
Results First Received: May 7, 2014
Last Updated: June 25, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Pemetrexed
Vinblastine
Vinorelbine
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014