a phase i/ii study of carboplatin and etoposide with or without obatoclax in extensive-stage small cell lung cancer (es-sclc)

Conditions: Extensive-stage Small Cell Lung Cancer

Summary: the phase i portion of this protocol will determine the best phase ii dose and schedule of obatoclax with carboplatin and etoposide in patients with extensive-stage small cell lung cancer. the phase ii portion will evaluate the response rate to this regimen.

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.

Eligibility criteria:
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

Keywords: es-sclc obatoclax