Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Metastatic Small Cell Lung Carcinoma

NGR007: A Phase II Study of NGR-hTNF Administered in Combination With Doxorubicin Every 3 Weeks in Patients Affected by Advanced or Metastatic Small Cell Lung Carcinoma (SCLC) Previously Treated With at Least One Therapeutic Regimen

The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic small cell lung carcinoma (SCLC) patients previously treated with at least one therapeutic regimen

This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic SCLC, previously treated with at least one therapeutic regimen, that will be conducted using Simon's two-stage design method.

Inclusion Criteria:

• Patients ≥ 18 years affected by SCLC previously treated with at least one therapeutic regimen (including doxorubicin). However, in case of patient already pretreated with doxorubicin, a previous cumulative dose of doxorubicin < 300 mg/m^2 is recommended and the current treatment has to be stopped when a maximum cumulative dose of doxorubicin 550 mg/m^2 is reached.

• Cytology or histology confirmed SCLC at first diagnosis (patient with recurrent disease do not require a confirmatory biopsy to be eligible)

• Measurable disease, defined as ≥ 1 unidimensional measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by CT scan according to RECIST criteria

• ECOG Performance status 0 - 2

• Adequate baseline bone marrow, hepatic and renal function, defined as follows:

  • Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L
  • Bilirubin < 1.5 x ULN
  • AST and/or ALT < 2.5 x ULN in absence of liver metastasis
  • AST and/or ALT < 5 x ULN in presence of liver metastasis
  • Serum creatinine < 1.5 x ULN

• Normal cardiac function (LVEF ≥ 55%) and absence of uncontrolled hypertension

• Patients may have had prior therapy providing the following conditions are met:

  - Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out period of 28 days before start treatment

  - Surgery: wash-out period of 14 days before start treatment

• Patients must give written informed consent to participate in the study

Exclusion Criteria:

• Concurrent anticancer therapy
• Patients may not receive any other investigational agents while on study
• Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
• Uncontrolled hypertension
• Prolonged QTc interval (congenital or acquired)
• Patient with significant peripheral vascular disease
• Previous signs of cardiotoxicity doxorubicin related
• Clinical signs of CNS involvement
• Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
• Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
• Known hypersensitivity/allergic reaction or contraindications to anthracyclines
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
• Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.