A Trial of Amrubicin and Carboplatin With Pegfilgrastim in Patients With Extensive-Stage Small Cell Lung Cancer

Inclusion criteria

• Cytologically and/or histologically confirmed small-cell lung cancer with extensive stage disease.
• Measurable or evaluable disease per RECIST criteria version 1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
• QTc interval of ≤450 msec. on ECG.
• Adequate organ function, including the following:

• ANC ≥1500 cells/micro liter
• Platelet count ≥100,000 cells/micro liter
• Hemoglobin ≥9 g/dL
• Total bilirubin ≤1.5 x ULN; AST/ALT ≤2.5 x ULN, (except if due to hepatic metastases, then ≤5 x ULN)
• Serum creatinine ≤1.5 x ULN
• Patients must be able to receive growth factors (G-CSF).
• Women of childbearing potential must have a negative serum or urine pregnancy test performed ≤ 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• Patients ≥18 years of age.
• Patients must be accessible for treatment and follow-up.
• Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion criteria

• Previous treatment for limited-stage SCLC.
• Previous chemotherapy or radiation therapy for SCLC (unless radiation was administered for brain metastases).
• Active brain metastases. Patients with treated brain metastases are eligible, if (1) radiation therapy was completed ≥ 21 days prior to first dose of amrubicin; (2) follow-up scan shows no disease progression; an absence of neurologic symptoms and (3) patient does not require steroids.
• Mixed small cell/non-small cell tumors or other neuroendocrine lung cancers.
• Women who are pregnant or breastfeeding.
• Suspected, diffuse idiopathic interstitial lung disease or pulmonary fibrosis.
• Patients with New York Heart Association (NYHA) class II or greater congestive heart failure (CHF).
• Any of the following ≤6 months prior to starting study treatment:

• myocardial infarction;
• severe unstable angina;
• ongoing cardiac dysrhythmia.
• Family history of idiopathic cardiomyopathy or uncontrolled heart arrhythmia.
• Treatment for other invasive cancers during the previous 5 years, or the presence of any active invasive cancer of any type (with the exception of non-melanoma skin cancers).
• Uncontrolled hypertension (i.e., blood pressure >150/90 mmHg that cannot be controlled with standard anti-hypertensive agents).
• Major surgical procedure or significant traumatic injury ≤ 28 days of study initiation.
• History of seropositive HIV or patients who are receiving immunosuppressive medications that would in the opinion of the investigator increase the risk of the serious neutropenic complications.
• Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Use of any non-approved or investigational agent ≤30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.