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

Gemin X

Status and phase: Completed; Phase 2; Phase 1

Conditions: Extensive-stage Small Cell Lung Cancer

Treatments: Drug: Obatoclax; Drug: Carboplatin/etoposide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00682981

GEM017

Details and patient eligibility

About

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.

Full 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.

Enrollment: 218 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

218 participants in 4 patient groups

Phase I A

Experimental group

Description:

Obatoclax for 3 hours for 3 days with carboplatin/etoposide.

Treatment:

Drug: Carboplatin/etoposide

Drug: Obatoclax

Phase I B

Experimental group

Description:

Obatoclax for 24 hours for 3 days with carboplatin/etoposide.

Treatment:

Drug: Carboplatin/etoposide

Drug: Obatoclax

Phase II A

Experimental group

Description:

Obatoclax for 3 hours for 3 days with carboplatin/etoposide.

Treatment:

Drug: Carboplatin/etoposide

Drug: Obatoclax

Phase II B

Active Comparator group

Description:

Carboplatin/etoposide without continued study treatment

Treatment:

Drug: Carboplatin/etoposide