A Phase I/II Study of Carboplatin and Etoposide With or Without Obatoclax in Extensive-stage Small Cell Lung Cancer (ES-SCLC)

In the Phase I portion, both 3 hour and 24 hour infusions of obatoclax with carboplatin and etoposide every 3 weeks will be evaluated at different doses. In the Phase II portion, 3 hour infusions of obatoclax with or without carboplatin and etoposide every three weeks will be evaluated for response rates.

Inclusion criteria

Phase I:

• Pathological or cytological confirmation of SCLC
• ES-SCLC
• Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) with at least one lesion ≥2.0 cm using conventional technique or ≥1.0 cm with spiral computed tomography (CT) scan in a single dimension
• No previous chemotherapy
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
• Normal organ function defined as: absolute neutrophil count (ANC)

• 1500/mm3, platelets ≥100,000/mm3, total bilirubin ≤ upper limit of normal (ULN) or total bilirubin ≤ 3.0 if liver metastases are present, alanine aminotransferase (serum glutamic pyruvic transaminase) (ALT [SGPT])

• 2.5 ´ ULN or ALT/SGPT ≤ 5 ´ ULN if liver metastases are present, and creatinine within normal institutional limits or calculated creatinine clearance ≥50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Negative serum or urine pregnancy test result prior to study entry. In addition, women of child-bearing potential and men with partners of child-bearing potential must agree to use acceptable forms of birth control (those that result in less than 1% pregnancy/year when used correctly: implants, injectables, combined oral contraceptives, some IUDs, vasectomy of a male partner, sexual abstinence)
• Ability to understand and willingness to sign a written informed consent form

Phase II:

• Pathological or cytological confirmation of SCLC
• ES-SCLC
• Measurable disease using RECIST criteria with at least one lesion

• 2.0 cm using conventional technique or ≥1.0 cm with spiral CT scan in a single dimension
• No previous chemotherapy
• Age ≥18 years
• ECOG Performance Status ≤2;
• Normal organ function defined as: ANC ≥1500/mm3, platelets ≥100,000/mm3, total bilirubin ≤ULN or total bilirubin ≤ 3.0 if liver metastases are present, ALT (SGPT) ≤2.5 ´ ULN or ALT/SGPT ≤ 5 ´ ULN if liver metastases are present, and creatinine within normal institutional limits or calculated creatinine clearance ≥50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Negative serum or urine pregnancy test result prior to study entry. In addition, women of child-bearing potential and men with partners of child-bearing potential must agree to use acceptable forms of birth control (those that result in less than 1% pregnancy/year when used correctly: implants, injectables, combined oral contraceptives, some IUDs, vasectomy of a male partner, sexual abstinence)
• Ability to understand and willingness to sign a written informed consent form

Exclusion criteria

Phase I and II:

• Other investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
• History of allergic reactions attributed to components of the obatoclax formulation (Polysorbate 20 and PEG 300)
• History of seizure disorders unrelated to SCLC brain metastases, or presence of symptomatic brain metastases
• Uncontrolled,intercurrent illness including, but not limited to, symptomatic neurological illness; active, uncontrolled systemic infection considered opportunistic, lifethreatening,or clinically significant at the time of treatment; symptomatic congestive heart failure; unstable angina pectoris; clinically significant cardiac arrhythmia; significant pulmonary disease or hypoxia; or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women and women who are breast feeding;
• human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy