Study Using a Genomic Predictor of Platinum Resistance to Guide Therapy in Stage IIIB/IV Non-Small Cell Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cisplatin & Gemcitabine; Cisplatin & Pemetrexed; Docetaxel & Gemcitabine; Pemetrexed & Gemcitabine
Intervention description: Squamous Cell NSCLC:
Gemcitabine 1250 mg/m2 IV over 30 minutes day 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles; Non-Squamous Cell NSCLC:
Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles; Squamous Cell NSCLC:
Docetaxel 75 mg/m2 IV over 60 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles; Non-Squamous Cell NSCLC:
Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles
Intervention MeSH terms: Cisplatin; Gemcitabine; Docetaxel; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: genomics; genomics predictor; genomics analysis; squamous; non-squamous

Summary:

      In this trial, subjects with chemo-naive advanced non-small cell lung cancer (NSCLC) were
      assigned to chemotherapy using a genomic-based predictor for platinum sensitivity. After an
      amendment dated 1/25/2010, subjects with squamous cell NSCLC sensitive to cisplatin received
      cisplatin/gemcitabine and if resistant to cisplatin received docetaxel/gemcitabine. Subjects
      with non-squamous cell NSCLC sensitive to cisplatin received cisplatin/pemetrexed and if
      resistant to cisplatin received pemetrexed/gemcitabine. The primary objective of this trial
      was to prospectively validate the genomic-based prediction model through separate evaluation
      of the one-year progression-free survival (PFS) of the cisplatin-sensitive and
      cisplatin-resistant cohorts. Secondary objectives included: assessment of overall time to
      progressive disease, quality of life and evaluation of drug sensitivity patterns of cisplatin
      and pemetrexed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Suspected or histologic/cytologic select stage IIIB or IV NSCLC, not amenable to
             curative treatment with surgery or XRT. Histologic/cytologic documentation of
             recurrence required in patients who were previously completely resected and now have
             metastatic disease.

          -  Fresh frozen tissue must be available to generate and apply the genomics predictor. If
             not obtained at the time of diagnosis, then subject must consent to another biopsy as
             a fresh tissue sample must yield adequate high quality RNA. Patients with symptomatic
             brain metastases must complete brain XRT and be neurologically stable (steroids
             permitted) prior to research biopsy. If patient had prior XRT therapy, fresh frozen
             tissue biopsy for genomics analysis must be outside XRT field.

          -  At least one, non-radiated, measurable lesion by RECIST criteria.

          -  ECOG performance status of 0 or 1.

          -  NO prior chemo, biologic or targeted therapy for any malignancy. Prior therapy with
             low dose methotrexate or similar medications allowed if used for non-malignant
             conditions.

          -  Prior XRT therapy is permitted if ≥1 week since completion of XRT (≥2 weeks for whole
             brain XRT). XRT must be <25% of bone marrow reserve.

          -  Age ≥18 years.

          -  No previous or concomitant malignancy in past 5 years other than surgical management
             for carcinoma in situ of the cervix, breast, NSCLC, basal cell or squamous cell
             carcinoma of the skin.

          -  No other serious medical or psychiatric illness.

          -  Signed informed consent.

          -  Required lab data within 2 weeks of enrollment:

               1. ANC/AGC ≥1500 per uL

               2. Platelets ≥100,000 per uL

               3. Total bili ≤1.5 mg/dL

               4. Creatinine ≤2 mg/dL; creatinine clearance ≥45 ml/min.

               5. SGOT/SGPT ≤3x ULN except in presence of known hepatic mets (may be up to 5x ULN)
                  unless receive docetaxel/gemcitabine than SGOT/SGPT ≤1.5x ULN.

          -  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 determine by the patient and their health care
             team, during study and for 3 months following the last dose of study drug.

        Exclusion Criteria:

          -  Treatment within the last 30 days with a drug that has not received regulatory
             approval for any indication at the time of study entry.

          -  Concurrent administration of any other anti-tumor therapy (see #5 inclusion for
             exceptions).

          -  Inability to comply with protocol or study procedures.

          -  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.

          -  Untreated CNS metastases unless brain XRT completed and neurologically stable
             (steroids permitted).

          -  Major surgery within 2 weeks of study or other serious concomitant systemic disorders
             that would compromise the safety of the patient or patient's ability to complete the
             study.

          -  MI having occurred less than 6 months before inclusion, any known uncontrolled
             arrhythmia, symptomatic angina pectoris, active ischemia or cardiac failure not
             controlled by meds.

          -  Contraindications to corticosteroids.

          -  Inability/unwillingness to take folic acid or vitamin B12.

          -  Unwillingness to stop taking herbal supplements while on study.

          -  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 treatment initiation and throughout study enrollment.

          -  Inability to discontinue aspirin at a dose >1300 mg/day or other non-steroidal
             anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of
             pemetrexed (5 days for long-acting agents such as piroxicam).

          -  Female patients that are pregnant or breast-feeding.