AMR PH GL 2007 CL001 Phase 3 Trial in Patients With Small Cell Lung Cancer After Failure of First-Line Chemotherapy

• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of objective response rate [ Time Frame: Until death ] [ Designated as safety issue: No ]
• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of progression-free survival. [ Time Frame: Until death ] [ Designated as safety issue: No ]
• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of duration of response [ Time Frame: Until death ] [ Designated as safety issue: No ]
• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of time to tumor progression [ Time Frame: Until death ] [ Designated as safety issue: No ]
• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of safety [ Time Frame: Until death ] [ Designated as safety issue: Yes ]
• To further characterize the clinical benefit of amrubicin compared with topotecan in terms of quality of life [ Time Frame: Until death ] [ Designated as safety issue: No ]

This study drug (Amrubicin) is believed to work by stopping the tumor cells in your body from growing. The purpose of this study is to evaluate the effect of amrubicin compared to topotecan in the treatment of small cell lung cancer.

Small cell lung cancer represents approximately 13% of the cancers of the lung and presents as extensive stage disease in 60% to 70% of patients. Sites of metastases include bone (35%), liver (25%), bone marrow (20%), brain (10%), extrathoracic lymph nodes (5%), and subcutaneous masses (5%). Small-cell lung cancer has prominent markers of neuroendocrine differentiation.

The staging classification for SCLC is the 2-stage Veterans Administration Lung Study Group system that categorizes patients as having limited or extensive disease. Limited stage SCLC is disease confined to 1 hemithorax with or without adjacent mediastinal and/or supraclavicular lymph node involvement, but without a pleural effusion. This extent of disease can be included in a tolerable radiation field. Extensive-disease SCLC is any disease beyond the definition of limited-stage disease.

There are few proven treatment options for SCLC patients who fail first-line chemotherapy. New treatment strategies must be evaluated. The need to discover active agents with better toxicity profiles continues to be of great importance. Amrubicin may be an effective treatment for this population.

• Drug: Amrubicin
  Amrubicin for injection is supplied as 50-mg vials. Patients will receive 40 mg/m2 amrubicin as a 5-minute infusion once daily for 3 consecutive days starting on Day 1 of a 21-day course
  Other Name: amrubidin hydrochloride, Calsed, CNF3140
• Drug: Topotecan
  Topotecan for injection is supplied as 4-mg vials. Patients will receive 1.5 mg/m2 as a 30-minute infusion once daily for 5 consecutive days starting on Day 1 of a 21-day course
  Other Name: Topotecan hydrochloride, Hycamtin

• Experimental: Amrubicin
  Amrubicin
  Intervention: Drug: Amrubicin
• Active Comparator: Topotecan
  Topotecan
  Intervention: Drug: Topotecan

Inclusion Criteria:

• Histological or cytological diagnosis of SCLC at study entry according to the International Association for the Study of Lung Cancer (IASLC) histopathologic classification. Mixed or combined subtypes according to the IASLC are not allowed;
• SCLC that is either sensitive (defined as a response including stable disease to first-line platinum-based chemotherapy, with subsequent progression >/= 90 days after completing first-line chemotherapy) or refractory (defined as best response to first-line platinum-based chemotherapy or progression < 90 days after completing first-line chemotherapy);
• Extensive or limited disease; patients with limited disease who are candidates for local or regional salvage radiation therapy must have been offered such treatment prior to participation in this study;
• Radiographically documented progression after first-line treatment with platinum-based chemotherapy;
• No more than 1 prior chemotherapy regimen;
• At least 18 years of age;
• ECOG performance status of 0 - 1

Exclusion Criteria:

• Chest radiotherapy with curative intent to the primary disease complex </= 28 days prior to first dose; CNS radiotherapy </= 21 days prior to first dose; radiotherapy to all other areas </= 7 days prior to first dose;
• Prior anthracycline, topotecan, or irinotecan treatment.
• Prior anthracycline or topotecan treatment.
• Patients with know history of seropositive human immunodeficiency virus (HIV) or patients who are receiving immunosuppressive medications that would increase the risk of serious neutropenic complications