Intervention: Irinotecan
Trial phase: Phase 1 | Phase 2
ATC code: L01CE02 | L01XX19
SMILES: CCc1c2c(nc3ccc(OC(=O)N4CCC(N5CCCCC5)CC4)cc13)-c1cc3c(c(=O)n1C2)COC(=O)[C@]3(O)CC
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 30
Group description: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

Novel Drug Combination: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

•All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
Eligibility criteria:
Inclusion Criteria:

Histologic or cytologic diagnosis of extensive stage SCLC.
Measurable or assessable tumor parameters.
ECOG Performance Status 0-2.
Age between 18 and 79 years (in the State of Alabama > 18).
Adequate bone marrow, liver and renal function, defined as:
Absolute neutrophil count (ANC) ≥ 1500/µL
Hemoglobin ≥ 8g/dl
Platelet count ≥ 100,000/µL
SGOT/SGPT ≤ 2 x upper limit of normal or ≤ 5 x upper limit of normal when liver metastases are present.
Total bilirubin value ≤ 2 x upper limit of normal.
Serum creatinine value ≤ 2 x upper limit of normal.
Fully recovered from any previous surgery (at least 4 weeks since major surgery)
Must have recovered from prior radiation therapy (at least 3 weeks)
All subjects must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential.
Must provide written informed consent and authorization to use and disclose health information (HIPAA).
Extensive-stage SCLC as defined as disease not confined to one hemithorax, including ipsilateral pleural effusion or pericardial effusion.
No prior chemotherapy.

Exclusion Criteria:

Concurrent cancer chemotherapy, biologic therapy or radiotherapy.
Administration of any investigational drug within 28 days prior to administration of the current therapy.
Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery.
Concurrent serious infection.
Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise patient safety and affect the outcome of the study.
History of other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for a minimum of 2 years.
Neuropathy at baseline ≥ Grade 2.
Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial.
History of chronic diarrhea; or diarrhea (excess of 2-3 stools/day above normal frequency) in the past 2 weeks.
History of a positive serology for human immunodeficiency virus (HIV).
Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions.
Pregnant or lactating women.