Cisplatin, Irinotecan and Bevacizumab (NSC #704865, IND #7921) for Untreated Extensive Stage Small Cell Lung Cancer: A Phase II Study

Inclusion Criteria:

- All patients must have histologically or cytologically documented small cell
carcinoma of the bronchus

- The extensive disease classification for this protocol includes all patients with
disease sites not defined as limited stage; limited stage disease category includes
patients with disease restricted to one hemithorax with regional lymph node
metastases, including hilar, ipsilateral and contralateral mediastinal, and/or
ipsilateral supraclavicular nodes; extensive stage patients are defined as those
patients with extrathoracic metastases, malignant pleural effusion, bilateral or
contralateral supraclavicular adenopathy or contralateral hilar adenopathy

- Measurable or Non-measurable Disease

- No prior chemotherapy or investigational therapy for SCLC

- Radiation therapy must have been completed at least three weeks before initiation of
protocol therapy

- No major surgical procedure within 28 days prior to starting treatment and fully
recovered

- No minor surgical procedure (mediastinoscopy or core biopsy) within 7 days prior to
starting treatment

- ECOG performance status: 0-2

- No "currently active" second malignancy other than non-melanoma skin cancers

- No CNS metastases; patients with a history of CNS metastases will NOT be eligible
even if they have completed a course of CNS radiotherapy; all patients will have a
screening brain CT or MRI to rule out occult CNS metastases

- No recent history of CVA (within 6 months)

- No serious or non-healing wound ulcer or bone fracture

- Patients with a history of significant bleeding episodes (e.g., hemoptysis, bleeding
diathesis, upper or lower GI bleeding) are not eligible; patients with trace blood in
the sputum ("blood tinged sputum") are eligible

- No myocardial infarction or significant change in anginal pattern within one year or
current congestive heart failure (NYHA Class 2 or higher)

- Patients with a history of hypertension must be well controlled (< 150/90) on a
stable regimen of anti-hypertensive therapy

- No HIV-positive patients receiving combination anti-retroviral therapy because of
possible pharmacokinetic interactions with the protocol treatment; (patients with
immune deficiency are at an increased risk of lethal infections when treated with
marrow-suppressive therapy)

- No chronic daily treatment with aspirin (> 325 mg/day) or on non-steroidal
antiinflammatory agents known to inhibit platelet function; no treatment with
dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), cilostazol
(Pletal), or other antiplatelet agents

- No clinically significant peripheral neuropathy (grade >= 2)

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No treatment with therapeutic anticoagulation; prophylactic anticoagulation for
central venous access devices is allowed provided requirements of INR < 1.5 and PTT <
1.2 x ULN are met; caution should be taken in treating patients with low dose heparin
or low molecular weight heparin for DVT prophylaxis as there may be an increased
bleeding risk with bevacizumab

- No current and/or recent (within 1 month) use of a thrombolytic agent; low dose
thrombolytic therapy for maintenance of central venous catheter is allowed

- No clinically significant peripheral arterial disease

- Non-pregnant and non-nursing; the effect of the combination of bevacizumab,
cisplatin, and irinotecan on the fetus and infant is unknown

- Granulocytes >= 1,500/μl

- Platelets >= 100,000/μl

- Serum Creatinine =< ULN

- Total Bilirubin < 2.0 mg/dl

- SGOT < 2 x ULN

- INR < 1.5

- PTT < 1.2 x ULN

- Urine protein (dipstick) < 1+