Carboplatin, Pemetrexed Disodium, and Bevacizumab in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Northwestern University

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Drug: pemetrexed

Biological: bevacizumab

Drug: carboplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00234052

NU-04L2

NU 04L2

STU00007415 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as carboplatin and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 tumor cells by blocking blood flow to the tumor. Giving carboplatin and pemetrexed disodium together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and pemetrexed disodium together with bevacizumab works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Full description

OBJECTIVES:

Primary

Determine the median time to disease progression in patients with stage IIIB or IV or recurrent non-squamous cell non-small cell lung cancer treated with carboplatin, pemetrexed disodium, and bevacizumab.

Secondary

Determine the response rate and duration of response in patients treated with this regimen.
Determine the toxic effects of this regimen in these patients.
Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with complete response, partial response, or stable disease continue to receive pemetrexed disodium and bevacizumab in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Enrollment

51 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically* or cytologically* confirmed non-small cell lung cancer
- Any histology, except squamous cell carcinoma, allowed
  - Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible
- No histology in close proximity to a major vessel or cavitation NOTE: *Histologic or cytologic elements may be established on metastatic tumor aspirates or biopsy
Meets 1 of the following stage criteria:
- Stage IIIB disease (with malignant pleural effusion)
- Stage IV disease
- Recurrent disease
Measurable or non-measurable disease
No known CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
No history of hemorrhagic disorders

Hepatic

Bilirubin < 1.5 mg/dL
AST and ALT < 5 times upper limit of normal
INR < 1.5
PTT normal

Renal

Creatinine clearance ≥ 45 mL/min
Urine protein:creatinine ≤ 1.0 by spot urinalysis

Cardiovascular

No myocardial infarction within the past 6 months
No New York Heart Association class II-IV congestive heart failure
No unstable angina pectoris
No serious cardiac arrhythmia requiring medication
No stroke within the past 6 months
No peripheral vascular disease ≥ grade 2
No uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg)
- Patients with a history of hypertension allowed provided blood pressure is well controlled on a stable regimen of anti-hypertensive therapy
No history of thrombotic disorders
No other clinically significant cardiovascular disease

Pulmonary

No history of gross hemoptysis, defined as bright red blood of a ½ teaspoon or more

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Must be willing and able to take daily oral folic acid, intermittent vitamin B_12 injections, and corticosteroid premedication
No ongoing or active infection
No serious, non-healing wound, ulcer, or bone fracture
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 3 weeks since prior immunotherapy

Chemotherapy

No prior systemic chemotherapy

Endocrine therapy

More than 3 weeks since prior hormonal therapy

Radiotherapy

See Disease Characteristics
More than 3 weeks since prior radiotherapy

Surgery

More than 4 weeks since prior major surgery
More than 1 week since prior minor surgery, fine needle aspiration, or core biopsy
No concurrent major surgery

Other

Recovered from all prior therapy
More than 4 weeks since prior and no concurrent participation in another experimental drug study
No aspirin or other nonsteroidal anti-inflammatory drug (NSAID) 2 days before and 2 days after each pemetrexed disodium infusion (5 days before and 2 days after each pemetrexed disodium infusion for NSAIDs with a long half-life [e.g., naproxen, rofecoxib, or celecoxib])
No concurrent therapeutic anticoagulation
- Concurrent prophylactic anticoagulation for venous access devices allowed provided requirements for INR and PTT are met
No concurrent administration of any of the following:
- Chronic daily treatment with aspirin (> 325 mg per day)
- NSAIDs known to inhibit platelet function, including any of the following:
  - Dipyridamole
  - Ticlopidine
  - Clopidogrel
  - Cilostazol