A Phase I Followed by a Randomized, Phase II Study of Carboplatin and Etoposide With or Without Obatoclax Administered Every 3 Weeks to Patients With Extensive- Stage Small Cell Lung Cancer (ES-SCLC)

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