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

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00234052
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 51
• Locations: 5
• Arm: 1
• Actual Duration (Months): 76
• Patients Per Site: 10.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: bevacizumab; Drug: carboplatin; Drug: pemetrexed	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
• Actual Study Start Date: Jul 28, 2005
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Nov 28, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment Arm Carboplatin + pemetrexed + bevacizumab

Biological: bevacizumab; 5 mg/kg administered intravenously over 90 minutes on day 1 of each cycle (cycle = 3 weeks); Other Names: Avastin ; Drug: carboplatin; Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle (1 cycle = 3 weeks); Drug: pemetrexed; Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle (1 cycle = 3 weeks); Other Names: pemetrexed disodium

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival [Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months)]

   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.

Secondary Outcome Measures

1. Overall Response Rate [Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months)]

   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.

2. Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment [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)]

   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

3. Overall Survival Rate [During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death.]

   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.

4. Duration of Response [From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
2	Rush Cancer Institute at Rush University Medical Center	Chicago	Illinois	United States	60612
3	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
4	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
5	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174

Sponsors and Collaborators

• Northwestern University
• National Cancer Institute (NCI)

Investigators

• Study Chair: Jyoti D. Patel, Robert H. Lurie Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00234052
• Other Study ID Numbers: NU 04L2; NU-04L2; STU00007415
• First Posted: Oct 6, 2005
• Last Update Posted: Jun 4, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Northwestern University: 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
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Bevacizumab; Carboplatin; Pemetrexed

Study Results

Participant Flow

Recruitment Details	The study opened for accrual on June 1, 2005 with an accrual goal of 50 patients. The first patient enrolled started treatment on July 28, 2005. The study was closed permanently on July 10, 2007 when accrual had been met with 51 patients registered and 50 patients treated on study.

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Period Title: Treatment
STARTED	51
Started Treatment	50
Completed 6 Cycles	33
Went Into Maintenance Phase	30
COMPLETED	30
NOT COMPLETED	21
Period Title: Treatment
STARTED	50
COMPLETED	1
NOT COMPLETED	49

Baseline Characteristics

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Overall Participants	51
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 54.9%
>=65 years	23 45.1%
Sex: Female, Male (Count of Participants)
Female	28 54.9%
Male	23 45.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 3.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 9.8%
White	41 80.4%
More than one race	0 0%
Unknown or Not Reported	3 5.9%
Region of Enrollment (participants) [Number]
United States	51 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival
Description	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.
Time Frame	Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	50
Median (95% Confidence Interval) [Months]	7.8

2. Secondary Outcome

Title	Overall Response Rate
Description	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.
Time Frame	Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months)

Outcome Measure Data

Analysis Population Description

One patient received less than one cycle and was determined to not be evaluable for this outcome measure.

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	49
Count of Participants [Participants]	27 52.9%

3. Secondary Outcome

Title	Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment
Description	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
Time Frame	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)

Outcome Measure Data

Analysis Population Description

This includes AEs observed before there was an amendment of the protocol to exclude patients with histories of diverticulitis or clinically significant diverticular disease. Any patient that received one dose of study drug is evaluable for this objective.

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	50
Anemia	3 5.9%
Thrombocytopenia	4 7.8%
Neutropenia	2 3.9%
Venous Thrombosis	3 5.9%
Fatigue	4 7.8%
Diverticulitis	4 7.8%
Infection	5 9.8%
Proteinuria	1 2%
Arterial Thrombosis	1 2%
Increased Creatinine Levels	1 2%

4. Secondary Outcome

Title	Overall Survival Rate
Description	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.
Time Frame	During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	50
Median (95% Confidence Interval) [Months]	14.1

5. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51.

Outcome Measure Data

Analysis Population Description

Patients with response were included in this outcome measure.

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	27
Median (95% Confidence Interval) [Months]	7.7

6. Post-Hoc Outcome

Title	Progression Free Survival at 6, 12, 18, 24 Months
Description	Progression Free Survival (PFS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment is defined as the percentage of patients without progression at the following time points from registration to the study: 6 months 12 months 18 months 24 months.
Time Frame	6, 12,18, and 24 months from treatment initiation

Outcome Measure Data

Analysis Population Description

One patient received less than one cycle and was determined to not be evaluable for this objective.

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	50
6 Months	59
12 Months	34
18 Months	27
24 Months	19

7. Post-Hoc Outcome

Title	Overall Survival Rate at 6, 12, 18, and 24 Months
Description	Overall Survival (OS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment will be defined as the percentage of patients with documentation of status of alive at the following timepoints from registration to the study: 6 months 12 months 18 months 24 months
Time Frame	6, 12,18, and 24 months from treatment initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
Measure Participants	50
6 Months	86
12 Months	61
18 Months	38
24 Months	26

Adverse Events

Time Frame	Adverse events were collected from the start of treatment, every cycle, until 30 days post the last treatment where one cycle equals 21 days. Range of cycles completed by patients = 1 cycle to 51 cycles.
Arm/Group Title	Treatment With Carboplatin + Pemetrexed + Bevacizumab
Arm/Group Description	Carboplatin + Pemetrexed + Bevacizumab Patients will receive 6 cycles where (1 cycle is 21 days) of : Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Carboplatin: Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle Patients without progression will go into the maintenance phase and receive cycles of the following where 1 cycle is 21 days: Bevacizumab: 15 mg/kg administered intravenously over 30 - 90 minutes on day 1 of each cycle Pemetrexed: Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle
All Cause Mortality
	Treatment With Carboplatin + Pemetrexed + Bevacizumab
	Affected / at Risk (%)	# Events
Total	41/50 (82%)
Serious Adverse Events
	Treatment With Carboplatin + Pemetrexed + Bevacizumab
	Affected / at Risk (%)	# Events
Total	22/50 (44%)
Blood and lymphatic system disorders
Thrombocytopenia	1/50 (2%)
Cardiac disorders
Heart Attack	1/50 (2%)
Cardiomyopathy	1/50 (2%)
Gastrointestinal disorders
Bowel Obstruction	1/50 (2%)
Acute and Chronic Cholelithiasis	2/50 (4%)
Diverticulitis	4/50 (8%)
Vomiting	1/50 (2%)
General disorders
Epistaxis	2/50 (4%)
Infections and infestations
Osteomylitis of the right great toe	1/50 (2%)
Pneumonia	1/50 (2%)
Axillary Abscess	1/50 (2%)
Viral Pneumonitis resulting in Death	1/50 (2%)
Pneumonia/death	1/50 (2%)
Musculoskeletal and connective tissue disorders
Puesdogout	1/50 (2%)
Nervous system disorders
Seizures	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/50 (2%)
Dyspnea	2/50 (4%)
Bronchitis	1/50 (2%)
Other (Not Including Serious) Adverse Events
	Treatment With Carboplatin + Pemetrexed + Bevacizumab
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Neutrophils (Neutropenia)	6/50 (12%)
Hemoglobin (Anemia)	30/50 (60%)
Platelets (Thrombocytopenia)	11/50 (22%)
Cardiac disorders
Hypertension	20/50 (40%)
Eye disorders
Watery Eye	3/50 (6%)
Gastrointestinal disorders
Anorexia	7/50 (14%)
Constipation	15/50 (30%)
Diarrhea	12/50 (24%)
Mucositis/Stomatitis	13/50 (26%)
Nausea	22/50 (44%)
Vomiting	11/50 (22%)
General disorders
Fatigue	43/50 (86%)
Fever	4/50 (8%)
Insomnia	3/50 (6%)
Weight Loss	10/50 (20%)
Epistaxis (Nosebleed)	8/50 (16%)
Pain NOS	25/50 (50%)
Infections and infestations
Infection NOS	4/50 (8%)
Metabolism and nutrition disorders
Alkaline Phosphastase Increase	8/50 (16%)
Transaminase	6/50 (12%)
ALT Increase	4/50 (8%)
AST Increase	5/50 (10%)
Albumin Decrease	5/50 (10%)
Creatinine, Serum-high	9/50 (18%)
Calcium, Serum-low (Hypocalcemia)	3/50 (6%)
Glucose, Serum-high (Hyperglycemia)	18/50 (36%)
Proteinuria	4/50 (8%)
Musculoskeletal and connective tissue disorders
Back Pain	4/50 (8%)
Nervous system disorders
Neuropathy: Sensory	5/50 (10%)
Dizziness	3/50 (6%)
Mood Alteration - Anxiety	5/50 (10%)
Headache	9/50 (18%)
Renal and urinary disorders
Urinary Tract Infection NOS	3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	5/50 (10%)
Dyspnea (Shortness of Breath)	24/50 (48%)
Skin and subcutaneous tissue disorders
Hair loss/Alopecia (scalp or body)	6/50 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.