Study of Amrubicin in Patients With Small Cell Lung Cancer Refractory or Progressive to Prior Therapy

A Phase 2 Trial of Single-Agent Amrubicin in Patients With Extensive Disease Small Cell Lung Cancer That is Refractory or Progressive Within 90 Days of Completion of First Line Platinum-based Chemotherapy

The purpose of the study is to evaluate the objective tumor response rate of amrubicin when administered as second-line therapy to ED-SCLC patients who have refractory or progressive disease.

Inclusion Criteria:

• Histological or cytological diagnosis of SCLC; extensive-disease (ED) at time of study entry

• Refractory to first-line platinum-based chemotherapy (i.e., has received one prior platinum-based chemotherapy regimen) defined as one of the following:

  • Best response to first-line chemotherapy is radiographically documented progression (refractory disease)
  • Best response to first-line chemotherapy is radiographically documented response or stable disease, with subsequent documented progression during continuing chemotherapy (resistant relapse)
  • Documented progression within 90 days of completion of first-line chemotherapy (last dose of chemotherapy), regardless of best response to treatment (resistant relapse)

• At least 18 years of age

• ECOG Performance Status of 0, 1, or 2

• Measurable disease defined by RECIST criteria

  • Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology and/or cytology.
  • Measurable lesion: Lesions that can be accurately measured in at least one dimension with the longest diameter ≥20mm using conventional techniques or ≥10mm using spiral CT scans.

• CT (including spiral CT) scans and MRI are the preferred methods of measurement; however, chest x-rays are acceptable if the lesions are clearly defined and surrounded by aerated lung. Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes). For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required.

• Adequate organ function including the following:

  • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1500 cells/μL, platelet count ≥100,000 cells/μL and hemoglobin ≥9g/dL.
  • Hepatic: bilirubin ≤ 1.5 X ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 X ULN.
  • Renal: serum creatinine < 2.0 mg/dL or calculated creatinine clearance >60 mL/min.
  • Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA or echocardiography (intra-patient reassessment of LVEF should be performed via the same method throughout the study).

• Negative serum pregnancy test at the time of enrollment for women of child-bearing potential. For men and women of child-bearing potential, use of effective contraceptive methods during the study.

• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.

Exclusion Criteria:

• Pregnant or nursing women
• Chest radiotherapy within the previous 28 days or other radiotherapy within the previous 14 days. Recovery from the acute toxic effects of radiation required prior to study enrollment. Measurable lesions that have been previously irradiated must be enlarging to be considered target lesions. Prior radiation therapy allowed to < 25% of the bone marrow.
• More than 1 prior chemotherapy regiment for SCLC
• Prior anthracycline treatment
• Treatment with any investigational agent within 28 days or standard chemotherapy within 21 days prior to first dose. Patients must have recovered from all acute adverse effecxts of prior therapies, excluding alopecia
• Patients with secondary primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 2 years previously with surgery and/or radiotherapy and no evidence of recurrence since that time)
• Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
• Symptomatic central nervous system metastases. Patients with asymptomatic brain metastases are allowed. The patient must be stable after radiotherapy for ≥ 2 weeks and off corticosteroids for ≥ 1 week.
• History of interstitial lung disease or pulmonary fibrosis.