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

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Phase I B	Obatoclax	Obatoclax for 24 hours for 3 days with carboplatin/etoposide.
Phase I A	Carboplatin/etoposide	Obatoclax for 3 hours for 3 days with carboplatin/etoposide.
Phase II B	Carboplatin/etoposide	Carboplatin/etoposide without continued study treatment
Phase II A	Carboplatin/etoposide	Obatoclax for 3 hours for 3 days with carboplatin/etoposide.
Phase I B	Carboplatin/etoposide	Obatoclax for 24 hours for 3 days with carboplatin/etoposide.
Phase I A	Obatoclax	Obatoclax for 3 hours for 3 days with carboplatin/etoposide.
Phase II A	Obatoclax	Obatoclax for 3 hours for 3 days with carboplatin/etoposide.

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method

Locations (75): Clearview Cancer Institute
🇺🇸
Huntsville, Alabama, United States
Northwest Alabama Cancer Center
🇺🇸
Muscle Shoals, Alabama, United States
Mayo Clinic-Arizona
🇺🇸
Scottsdale, Arizona, United States
Arizona Clinical Research Center
🇺🇸
Tucson, Arizona, United States
City of Hope and Beckman Research Institute
🇺🇸
Duarte, California, United States
University of California-San Diego Moores Cancer Center
🇺🇸
LaJolla, California, United States
Georgetown University Hospital-Lombardi Comprehensive Cancer Center
🇺🇸
Washington, District of Columbia, United States
Integrated Community Oncology Network
🇺🇸
Jacksonville, Florida, United States
University of Miami-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Florida Cancer Institute
🇺🇸
New Port Richey, Florida, United States
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Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States