Clinical trial NCT00234052: Carboplatin, Pemetrexed Disodium, and Bevacizumab in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-06
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Median Progression Free Survival
timeFrame: Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months)
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months)
measure: Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment
timeFrame: From treatment initiation, at the beginning of each cycle where one cycle equals 21 days until 30 days post treatment (range of cycles 1-51)
measure: Overall Survival Rate
timeFrame: During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death.
measure: Duration of Response
timeFrame: From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush Cancer Institute at Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare - Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Cancer Care Center
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Jyoti D. Patel
role: STUDY_CHAIR
References: