Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer
Condition: Non Squamous Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: OGX-427; Placebo
Intervention description: Three loading doses of 600mg OGX-427 will be administered intravenously (IV) during a 9 day period. Then 600mg IV OGX-427 will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive 600 mg IV OGX-427 plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.; Three loading doses of placebo will be administered intravenously (IV) during a 9 day period. Then placebo (IV) will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive placebo (IV) plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Recurrent Lung Cancer; Stage IV Lung Cancer; OGX-427; Sarah Cannon Research Institute; SCRI; OncoGenex; NSCLC; Non Small Cell Lung Cancer

Summary:

      This randomized phase II study will compare the efficacy and safety of the combination of
      carboplatin and pemetrexed with and without OGX-427 in patients with previously untreated
      advanced non-squamous NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologic or cytologic diagnosis of advanced NSCLC, excluding squamous cell and small
             cell histology. Tumors with mixed NSCLC histologies are eligible, as long as the
             predominant histology is not squamous. If small-cell elements are present or not
             otherwise specified histologically, the patient is not eligible.

          2. Metastatic disease (according to American Joint Committee on Cancer (AJCC) staging
             system, v7.0).

          3. No prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy
             for metastatic disease; previous adjuvant or neoadjuvant therapy for Stage I, II, or
             III disease is allowed as long as the interval from the end of treatment until disease
             progression was >12 months.

          4. No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow
             area. Other radiation therapy must be completed at least 2 weeks prior to study entry.
             Must have recovered from acute adverse effects prior to study entry.

          5. At least one measurable lesion according to Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1.

          6. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

          7. Baseline laboratory values as follows:

               -  Absolute neutrophil count (ANC) ≥1500/μL

               -  Hemoglobin (Hgb) ≥10 g/dL

               -  Platelets ≥100,000/μL

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the
                  upper limit of normal (ULN); 5 x ULN if known hepatic metastases.

               -  Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease

               -  Serum creatinine ≤1.5 x ULN. If creatinine is >1.5, calculate creatinine
                  clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method:

             Glomerular Filtration Rate (GFR) = (140-age) x (weight/kg) x (0.85 if female)/(72 x
             serum creatinine mg/dL)

          8. Fertile male patients willing to use adequate contraceptive measures.

          9. Female patients who are not of child-bearing potential, and fertile female patients of
             child-bearing potential who agree to use adequate contraceptive measures, who are not
             breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours
             prior to start of randomization.

         10. Life expectancy ≥ 12 weeks.

         11. Must be ≥18 years of age at the time of consent.

         12. Willingness and ability to comply with trial and follow-up procedures.

         13. Ability to understand the nature of this trial and give written informed consent.

        Exclusion Criteria:

          1. Known anaplastic lymphoma kinase (ALK) translocation and epidermal growth factor
             receptor (EGFR) "activating" mutations where first-line treatment with targeted
             tyrosine kinase inhibitor therapy is more appropriate.

          2. Known central nervous system (CNS) disease other than neurologically stable, treated
             brain metastases defined as metastasis having no evidence of progression or hemorrhage
             after treatment and no ongoing requirements for corticosteroids, (e.g., dexamethasone)
             for at least 2 weeks.

          3. Any of the following cardiac diseases currently or within the last 6 months as defined
             by New York Heart Association (NYHA) ≥ Class 2:

               -  Unstable angina pectoris

               -  Congestive heart failure

               -  Acute myocardial infarction

               -  Conduction abnormality not controlled with pacemaker or medication

               -  Significant ventricular or supraventricular arrhythmias (Patients with chronic
                  rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
                  are eligible).

          4. Patients currently receiving therapeutic anticoagulation.

          5. Pregnant or lactating women.

          6. Any serious, active underlying medical condition that would impair the ability of the
             patient to receive study treatment, such as diabetes mellitus or infection.

          7. Unable or unwilling to take folic acid or vitamin B12.

          8. Active second malignancy (except non-melanomatous skin or superficial bladder cancer)
             defined as requiring current need for cancer therapy or at high risk of recurrence
             (>30%) during the study.

          9. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

         10. Inability or unwillingness to comply with trial and/or follow-up procedures outlined
             in the protocol.