Extensive-stage Small Cell Lung Cancer
Conditions
Keywords
ES-SCLC, Obatoclax
Brief 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.
Detailed description
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.
Interventions
DRUGObatoclax
IV Infusions for 3 consecutive days of either 3-hours, 2 hours duration
Carboplatin/etoposide combination
Sponsors
Cephalon
Gemin X
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the recommended Phase II dose of obatoclax administered as a 3-hour or 24-hour infusion for 3 consecutive days in Phase I, and response rate in Phase II. | 6 months |
Countries
Bulgaria, Canada, Czechia, Hungary, India, Poland, Romania, Serbia, United Kingdom, United States
Outcome results
None listed