Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer
Condition: Small Cell Lung Cancer; Extensive Stage Lung Cancer; Chemonaive
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Small cell lung cancer, or SCLC, constitutes approximately 15% of the 170,000 new cases of
      lung cancer diagnosed annually in the United States. Extensive-stage SCLC comprises two
      thirds of new cases and is generally considered sensitive to chemotherapy, despite a median
      time to progression of 4 months. SCLC is one of the most aggressive and lethal types of
      cancer, with a median survival of 9 months (range 7-11 months) in patients diagnosed with
      extensive disease. Overall, the majority of patients with SCLC die in less than 2 years
      (2-year survival rates generally less than 10%), and the 5-year survival rate is 2.3% for
      patients with extensive disease. The regimen of etoposide in combination with a platinum
      (cisplatin or carboplatin) is generally considered the "standard of care" although a recent
      Phase III trial suggests improved survival with the combination of cisplatin/irinotecan.
      Further evaluation of new agents in combination regimens attempting to overcome the intrinsic
      drug resistance seen in extensive-stage SCLC is warranted attempting to improve survival and
      achieve palliation of disease-related symptoms.
    

Detailed description: 
      We are proposing a novel combination of bendamustine plus irinotecan followed by the standard
      regimen of etoposide with carboplatin. This will allow the investigation of response to the
      novel combination as well as any improvement in outcomes compared to historical controls.
    

Intervention name(s): Novel Drug Combination
Intervention type(s): Drug
Intervention description(s): This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.
All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks.
Other intervention name(s): Irinotecan (Camptosar); Carboplatin (Paraplatin); Etoposide (VdPesid); Bendamustine (Treanda)
Intervention MeSH terms: Carboplatin; Irinotecan; Etoposide; Bendamustine Hydrochloride
Intervention model: Single Group Assignment
Intervention model description: This is a single arm, open-label, Phase I - II trial with an initial dose escalation component and an expansion cohort of patients treated at the recommended Phase II dose.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Small cell lung cancer; Chemonaive; Bendamustine; Irinotecan; Etoposide; Carboplatin