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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Obatoclax
* Drug: Carboplatin/etoposide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I A<br>Obatoclax for 3 hours for 3 days with carboplatin/etoposide. | Drug: Obatoclax<br>* IV Infusions for 3 consecutive days of either 3-hours, 2 hours duration<br>* Other names: GX15-070MS;Drug: Carboplatin/etoposide<br>* Carboplatin/etoposide combination<br>* Other names: Control;|
| Experimental: Phase I B<br>Obatoclax for 24 hours for 3 days with carboplatin/etoposide. | Drug: Obatoclax<br>* IV Infusions for 3 consecutive days of either 3-hours, 2 hours duration<br>* Other names: GX15-070MS;Drug: Carboplatin/etoposide<br>* Carboplatin/etoposide combination<br>* Other names: Control;|
| Experimental: Phase II A<br>Obatoclax for 3 hours for 3 days with carboplatin/etoposide. | Drug: Obatoclax<br>* IV Infusions for 3 consecutive days of either 3-hours, 2 hours duration<br>* Other names: GX15-070MS;Drug: Carboplatin/etoposide<br>* Carboplatin/etoposide combination<br>* Other names: Control;|
| Active Comparator: Phase II B<br>Carboplatin/etoposide without continued study treatment | Drug: Carboplatin/etoposide<br>* Carboplatin/etoposide combination<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ES-SCLC, Obatoclax