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

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
carboplatin
pemetrexed
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
  • Rush Cancer Institute at Rush University Medical Center
  • Evanston Northwestern Healthcare - Evanston Hospital
  • Ingalls Cancer Care Center at Ingalls Memorial Hospital
  • Advocate Lutheran General Cancer Care Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

Carboplatin + pemetrexed + bevacizumab

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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.
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.

Full Information

First Posted
October 5, 2005
Last Updated
May 23, 2019
Sponsor
Northwestern University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00234052
Brief Title
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

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
July 28, 2005 (Actual)
Primary Completion Date
March 1, 2011 (Actual)
Study Completion Date
November 28, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northwestern University
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Carboplatin + pemetrexed + bevacizumab
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
5 mg/kg administered intravenously over 90 minutes on day 1 of each cycle (cycle = 3 weeks)
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle (1 cycle = 3 weeks)
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Other Intervention Name(s)
pemetrexed disodium
Intervention Description
Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle (1 cycle = 3 weeks)
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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)
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jyoti D. Patel
Organizational Affiliation
Robert H. Lurie Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-3013
Country
United States
Facility Name
Rush Cancer Institute at Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Evanston Northwestern Healthcare - Evanston Hospital
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201-1781
Country
United States
Facility Name
Ingalls Cancer Care Center at Ingalls Memorial Hospital
City
Harvey
State/Province
Illinois
ZIP/Postal Code
60426
Country
United States
Facility Name
Advocate Lutheran General Cancer Care Center
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068-1174
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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