Study of Sequential Topoisomerase, Irinotecan/Oxaliplatin - Etoposide /Carboplatin in Extensive Small Cell Lung Cancer (SCLC)
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of Part I of the study is to determine tumor response rate of
      sequential topoisomerase targeting with irinotecan/oxaliplatin followed by etoposide
      /carboplatin in chemotherapy-naïve patients with extensive small cell lung cancer. The
      primary objective of Part II of the study is to determine the objective tumor response rate
      of irinotecan/oxaliplatin in patients with either refractory disease or who have relapsed to
      first line chemotherapy or chemoradiotherapy.
    

Detailed description: 
      This is a Phase II, open label study for either chemotherapy-naïve patients with extensive
      SCLC or patients who are refractory or have relapsed to 1st line therapy for SCLC. The
      primary objective is to determine the objective response rate.

      This study consists of 2 parts:

      Part I - Chemotherapy-naïve patients with extensive SCLC

      • These patients will be treated with sequential topoisomerase targeting regimens (Regimen A
      and B). Regimen A consists of irinotecan and oxaliplatin (IROX), given on Day 1, and Neulasta
      administered on Day 2. Regimen B consists of etoposide and carboplatin, given on Day
      15(etoposide will be given daily x 3)and Neulasta on Day 18. Then, Regimen A will be given
      again 3 weeks later. The first re-evaluation for response will be performed 3 weeks after the
      second round of the sequential regimens.

      Schema of Part I:

      Regimen A (→ 2 weeks) Regimen B (→ 3 weeks) Regimen A (→ 2 weeks) Regimen B → (3 weeks) →
      Re-Stage

        -  The second re-evaluation for response will be performed 3 weeks after the fourth round
           of the sequential regimen. At this point patients with stable disease will be observed;
           those with either a partial or complete response will be treated with another round of
           sequential therapy (Regimen A → Regimen B) if there is no evidence of unacceptable
           toxicity. At the end (3 weeks after) of the fifth round of chemotherapy, patients will
           be re-evaluated for response, and will be followed-up for recurrent disease every 8
           weeks.

        -  Analysis of Top I and Top II levels in peripheral blood mononuclear cells will be
           performed in 10 patients of Part I.

        -  Evaluation of the expression of the ERCC genes (ERCC1, ERCC2, and XPF) will be performed
           in those patients in Part I with an adequate tumor specimen.

      Part II - Patients who have either refractory disease or have relapsed from 1st line therapy

      • These patients will be treated with Regimen A1 (IROX) at 3-week intervals. Neulasta will be
      administered on Day 2 of each cycle. The first re-evaluation for response will be performed 3
      weeks after the 3rd cycle of Regimen A1. The second re-evaluation for response will be
      performed 3 weeks after the 6th cycle of Regimen A1. At this point, patients with stable
      disease will be observed; those with either a partial or complete response will be treated
      with two additional cycles of Regimen A1 if there is no evidence of unacceptable toxicity. At
      the end (3 weeks after) of the 8th cycle of Regimen A1, patients will be re-evaluated for
      response, and will be followed-up for recurrent disease every 8 weeks.

      Schema of Part II:

      Regimen A1 (→ 3 weeks) Regimen A1 (→ 3 weeks) Regimen A1 (→ 3 weeks) Re-Stage
    

Intervention name(s): Intervention A: Irinotecan; Oxaliplatin; Neulasta; Intervention B: Etoposide; Carboplatin; Neulasta
Intervention type(s): Drug; Drug
Intervention description(s): Irinotecan (I.V.) 150-200 mg/m2; Day 1 (every 5 weeks) Oxaliplatin (I.V.) 85 mg/m2; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 1 (every 5 weeks); Etoposide (I.V.) 100 mg/m2; Day 1, 2, 3 (every 5 weeks) Carboplatin (I.V.) AUC 6; Day 1 (every 5 weeks) Neulasta (subcutaneous) 6 mg; Day 4 (every 5 weeks)
Other intervention name(s): Camptosar; Eloxatin; Pegfilgrastim; VP-16; Etopophos®; Vepesid®; Taxol; Paraplatin; Pegfilgrastim
Intervention MeSH terms: Carboplatin; Oxaliplatin; Irinotecan; Etoposide
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment