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

Lung Cancer Clinical Trial

Official title:

Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00234052
• Other study ID #: NU 04L2
• Secondary ID: NU-04L2STU000074
• Status: Completed
• Phase: Phase 2
• Start date: July 28, 2005
• Est. completion date: November 28, 2011

Study information

• Verified date: January 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: November 28, 2011
• Est. primary completion date: March 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• bevacizumab
5 mg/kg administered intravenously over 90 minutes on day 1 of each cycle (cycle = 3 weeks)

Drug:
• carboplatin
Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle (1 cycle = 3 weeks)
• pemetrexed
Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle (1 cycle = 3 weeks)

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois
United States	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Progression Free Survival	Progression Free Survival (PFS) in patients treated with the combination of carboplatin, pemetrexed and bevacizumab is defined as the time from registration to the time of documented disease progression or death from any cause. Patients that were lost to follow up or withdrew consent were censored at that point.	Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months)
Secondary	Overall Response Rate	Overall Response Rate (ORR) of patients treated with carboplatin, pemetrexed, and bevacizumab combination is defined as the number of patients who's best response is a Complete Response (CR) plus Partial Response (PR)as recorded from the start of treatment until disease progression as assessed by RECIST 1.0.; CR=Disappearance of all target lesions for a minimum of 4 weeks. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions for a minimum of 4 weeks, taking as reference the baseline sum LD. No simultaneous increase in the size of any lesion or the appearance of a new lesion may occur.	Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months)
Secondary	Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment	To characterize the toxicity profile of carboplatin, pemetrexed and bevacizumab combination treatment.; Toxicity data will be collected from initiation of treatment, every cycle, until 30 days post last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). Only toxicity determined to be a least possibility related to at least one study drug and grade 3 or 4 was collected for this outcome measure.; In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE	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)
Secondary	Overall Survival Rate	Overall Survival (OS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment is defined from the time of registration to the study until death from any cause. Patients that are lost to follow up will be censored from last documentation of survival status.	During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death.
Secondary	Duration of Response	Duration of Response for patients treated with the combination of carboplatin, pemetrexed and bevacizumab is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date of documented progressive disease.	From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51.