Cisplatin, Irinotecan, and Bevacizumab, in Treating Patients With Small Cell Lung Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Extensive Stage Small Cell Lung Cancer

Treatments

Drug: cisplatin

Other: laboratory biomarker analysis

Biological: bevacizumab

Drug: irinotecan hydrochloride

Study type

Interventional

Funder types

NIH

Identifiers

NCT00118235

NCI-2012-02815 (Registry Identifier)

CDR0000433341

U10CA031946 (U.S. NIH Grant/Contract)

P30CA014236 (U.S. NIH Grant/Contract)

CALGB-30306 (Other Identifier)

Details and patient eligibility

About

This phase II trial is studying how well giving cisplatin and irinotecan together with bevacizumab works in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of small cell lung cancer by blocking blood flow to the tumor. Giving cisplatin and irinotecan together with bevacizumab may kill more tumor cells.

Full description

PRIMARY OBJECTIVES:

I. To determine the percentage of patients with extensive stage small cell lung cancer treated with cisplatin, irinotecan and bevacizumab who live longer than 12 months.

SECONDARY OBJECTIVES:

I. To assess the response rate of patients treated with cisplatin, irinotecan and bevacizumab.

II. To evaluate the toxicity and tolerability of the combination of cisplatin, irinotecan and bevacizumab.

III. To determine the association between VEGF/KDR complex expression and VEGF plasma levels and tumor response.

OUTLINE:

Patients receive cisplatin IV over 60 minutes and irinotecan IV over 90 minutes on days 1 and 8. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 3 years.

Enrollment

72 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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+