Adjuvant Cisplatin With Either Genomic-Guided Vinorelbine or Pemetrexed for Early Stage Non-Small-Cell Lung Cancer
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Vinorelbine followed by Cisplatin; Pemetrexed followed by Cisplatin
Intervention description: 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).; 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)
Intervention MeSH terms: Cisplatin; Pemetrexed; Vinorelbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small-Cell Lung Cancer; NSCLC; Non-Squamous; Genomics; Guided Therapy; Directed Therapy; Genomic Expression Profiles; Chemotherapy Sensitivity

Summary:

      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.
    

Eligibility 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.