| | Requirement |
| 1 | Histologically or cytologically confirmed SCLC |
| 2 | Extensive disease, defined by at least one of the following criteria:
- No limited disease (i.e., no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field)
- Extrathoracic metastases
- Malignant pericardial or pleural effusion
- Contralateral hilar adenopathy |
| 3 | Measurable or non-measurable disease, as defined by modified RECIST |
| 4 | Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 |
| 5 | Life expectancy (with therapy) greater than or equal to 3 months |
| 6 | Woman or man greater than or equal to 18 years old |
| 7 | Patient must have signed and dated IRB approved informed consent and HIPAA authorization forms. |
| 8 | - Absolute neutrophil count (ANC) greater than or equal to 1,500
- Platelet count greater than or equal to 100,000
- Hemoglobin greater than or equal to 9 -Partial thromboplastin time (PTT) less than or equal to 1.3 x upper limit of normal (ULN) and international normalized ratio (INR) less than or equal to 1.3 - Creatinine (Cr) clearance (CrCl) greater than or equal to 60 - Aspartate aminotransferase (AST) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if attributable to liver metastases)
- Alanine aminotransferase (ALT) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if attributable to liver metastases) - Alkaline phosphatase less than or equal to 2.5 x ULN (less than or equal to 5 x ULN if attributable to bone and/or liver metastases)
- Total bilirubin less than or equal to 1.5 x ULN (less than or equal to 3 x ULN for subjects with UGT1A1 promoter polymorphism (i.e., Gilbert syndrome), confirmed by genotyping or Invader UGT1A1 molecular assay prior to enrollment) Fasting blood glucose less than or equal to 160 (Fasting will require subjects to refrain from all food and beverage [except water] for at least 8 hours) |
| 9 | Negative pregnancy test (urine or serum) within 7 days prior to enrollment (women of child-bearing potential only) |
| 1 | Symptomatic or untreated CNS metastasis
- Subjects with CNS metastases that are both treated and stably controlled are eligible if all of the following apply:
1. therapy has been administered (surgery and/or radiation therapy);
2. there is no additional treatment planned for brain metastases;
3. the subject is clinically stable; and
4. the subject is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment |
| 2 | Any prior or synchronous malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years prior to enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer |
| 3 | Prior chemotherapy, chemo-radiation or investigational agent for the treatment of SCLC
- Prior palliative radiotherapy to sites of distant metastasis is allowed (if completed greater than or equal to 7 days prior to enrollment)
- Prior treatment of CNS metastasis is allowed |
| 4 | Currently or previously treated with biological, immunological or other anti-tumor therapies for SCLC |
| 5 | Prior radiotherapy to > 25% of the bone marrow |
| 6 | Recent infection requiring systemic anti-infective treatment that was completed less than or equal to 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection) |
| 7 | Currently being treated with full dose anti-coagulation therapy (i.e. coumadin with a goal INR between 2 to 3, or full dose low molecular weight heparin) |
| 8 | History of bleeding diathesis |
| 9 | Current serious or non-healing wound or ulcer |
| 10 | Known positive test for human immunodeficiency virus, hepatitis C, chronic or active hepatitis B |
| 11 | Any clinically significant medical or psychiatric condition, co-morbid disease, addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic obstructive pulmonary disease), which may increase the risks associated with study participation or study treatments or could interfere with the safe delivery of study treatment or increase risk of toxicity |
| 12 | Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures |
| 13 | Major surgical procedure within 28 days prior to enrollment, or not yet recovered from major surgery |
| 14 | Minor surgical procedures within 7 days prior to enrollment, or not yet recovered from minor surgery
Note: uncomplicated placement of vascular access device greater than or equal to 1 day prior to first administration of study treatment, and fine needle aspiration, thoracocentesis or paracentesis greater than or equal to 3 days prior to first administration of study treatment is acceptable |
| 15 | Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction. |
| 16 | Inability to tolerate IV drug administration |
| 17 | Subject is currently enrolled in or has not yet completed at least 30 days prior to enrollment since ending other investigational device or clinical study(s) |
| 18 | Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic gonadotropin test) or is breast feeding |
| 19 | Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions i.e., double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 3 months after the last study drug administration for women, and 6 months for men |
| 20 | Subject has known sensitivity to any of the products to be administered during the study |
| 21 |
Subject unwilling or unable to comply with study requirements |
| 22 | Subject will not be available for follow-up assessments |
| 23 | Subject previously enrolled in this study |
