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Bevacizumab or Pemetrexed Disodium Alone or In Combination After Induction Therapy in Treating Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Sponsor
ECOG-ACRIN Cancer Research Group (Other)
Overall Status
Completed
CT.gov ID
NCT01107626
Collaborator
National Cancer Institute (NCI) (NIH)
1,516
Enrollment
434
Locations
3
Arms
132.2
Actual Duration (Months)
3.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 non-small cell lung cancer by blocking blood flow to the tumor. Pemetrexed disodium may stop the growth of tumor cells by blocking some enzymes needed for cell growth. It is not yet known whether giving bevacizumab or pemetrexed disodium alone or in combination is more effective in treating non-squamous non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying bevacizumab and pemetrexed disodium alone or in combination after induction therapy to see how well they work in treating patients with advanced non-squamous non-small cell lung cancer.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

OBJECTIVES:

Primary

  • To compare the overall survival (OS) of patients with advanced non-squamous non-small cell lung cancer (NSCLC) treated with maintenance therapy with bevacizumab vs pemetrexed disodium vs bevacizumab and pemetrexed disodium following induction therapy.

Secondary

  • To determine the response rate in patients treated with these regimens.

  • To evaluate the progression-free survival (PFS) of patients treated with these regimens.

  • To define the toxicity of these regimens in these patients.

  • To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA, and ERCC-118 TT in patients treated with induction therapy comprising paclitaxel, carboplatin and bevacizumab and determine the association between genotypes and response rate.

  • To determine the association between bevacizumab and pemetrexed disodium population pharmacokinetics and patient-specific covariate with bevacizumab or pemetrexed disodium toxicity.

  • To determine the frequency of TSER*3 polymorphisms in NSCLC and the association between TSER polymorphisms and benefit from pemetrexed disodium.

  • To evaluate TS and ERCC1 expression by RT-PCR and MTAP mutations in existing tumor specimens as a predictor of pemetrexed disodium response.

  • To evaluate polymorphisms within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 collectively or monogenically as markers for variation in efficacious and/or toxic response of individuals to treatment with taxanes.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to gender (male vs female), stage of disease (IIIB-T4Nx [with nodule in ipsilateral lung lobe and not candidate for combined chemotherapy and radiation] and IV M1a vs IV M1b vs recurrent), best response to first-time therapy (complete response/partial response vs stable disease), and smoking status (never vs smoker).

  • Induction therapy (Arm I): Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

  • Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Treatment begins within 6 weeks of the last day of induction chemotherapy administration.

  • Arm A: Patients receive bevacizumab IV over 30-90 minutes on day 1.

  • Arm B: Patients receive pemetrexed disodium IV over 10 minutes on day 1.

  • Arm C: Patients receive bevacizumab as in arm A and pemetrexed as in arm B. In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for correlative studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 2-5 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
1516 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC
Actual Study Start Date :
Aug 12, 2010
Actual Primary Completion Date :
Jan 31, 2019
Actual Study Completion Date :
Aug 17, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (Induction then Maintenance with Bevacizumab)

Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity.

Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • NSC 673089

    • Drug: Carboplatin
    Given IV
    Other Names:
  • carboplatin for injection or platinum diamine [1,1-cyclobutane-decarbozxylate (2-0,0')-,(SP-4-2)]

    • Biological: Bevacizumab
    Given IV
    Other Names:
  • NSC 704865
  • RhuMAb VEGF
  • Recombinant Humanized Monoclonal Anti-VEGF Antibody

    		•
    Experimental: Arm B (Induction then Maintenance with Pemetrexed)

    Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.

    Drug: Paclitaxel
    Given IV
    Other Names:
  • Taxol
  • NSC 673089

    • Drug: Carboplatin
    Given IV
    Other Names:
  • carboplatin for injection or platinum diamine [1,1-cyclobutane-decarbozxylate (2-0,0')-,(SP-4-2)]

    • Biological: Bevacizumab
    Given IV
    Other Names:
  • NSC 704865
  • RhuMAb VEGF
  • Recombinant Humanized Monoclonal Anti-VEGF Antibody

    • Drug: Pemetrexed Disodium Heptahydrate
    Given IV
    Other Names:
  • L-Glutamic acid
  • N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-
  • disodium salt
  • heptahydrate

    		•
    Experimental: Arm C (Induction then Maintenance with Bevacizumab & Pemetrexed)

    Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab as in arm A and pemetrexed as in arm B.

    Drug: Paclitaxel
    Given IV
    Other Names:
  • Taxol
  • NSC 673089

    • Drug: Carboplatin
    Given IV
    Other Names:
  • carboplatin for injection or platinum diamine [1,1-cyclobutane-decarbozxylate (2-0,0')-,(SP-4-2)]

    • Biological: Bevacizumab
    Given IV
    Other Names:
  • NSC 704865
  • RhuMAb VEGF
  • Recombinant Humanized Monoclonal Anti-VEGF Antibody

    • Drug: Pemetrexed Disodium Heptahydrate
    Given IV
    Other Names:
  • L-Glutamic acid
  • N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-
  • disodium salt
  • heptahydrate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5]

      Overall survival is defined as the time from randomization to death or date last known alive. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.

    Secondary Outcome Measures

    1. Progression-free Survival [Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5]

      Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is evaluated based on RECIST criteria and defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on current step. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.

    2. Response Rate [Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5]

      Response is evaluated based on RECIST criteria v1.1 and defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the current step's baseline sum diameters. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.

    Other Outcome Measures

    1. The Association Between Genotypes and Response Rate [Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5]

      To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA and ERCC-118 TT in patients with NSCLC receiving paclitaxel, carboplatin and bevacizumab therapy and determine the association between genotypes and response rate.

    2. The Association Between Bevacizumab and Pemetrexed Population Pharmacokinetics and Patient Specific Covariates With Bevacizumab or Pemetrexed Toxicity [Assessed every 3 weeks while on treatment and for 30 days after the end of treatment]

    3. The Frequency of TSER*3 Polymorphisms in NSCLC and the Association Between TSER Polymorphisms and Benefit From Pemetrexed [Assessed every 3 months for 2 years and every 6 months for years 3-5]

    4. The Association Between TS and ERCC1 Expression and Pemetrexed Response [Assessed every 3 months for 2 years and every 6 months for years 3-5]

    5. The Associations Between Polymorphisms Within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 Collectively or Monogenically and Efficacy and/or Toxicities [Assessed every 3 months for 2 years and every 6 months for years 3-5]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria (Step 1 Induction Therapy):

    • Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)

    • Predominant non-squamous histology (NSCLC not otherwise specified allowed). Mixed tumors are categorized by the predominant cell type.

    • Stage IV disease including M1a or M1b stages or recurrent disease

    • Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy

    • At least 12 months since prior adjuvant chemotherapy

    • At least 2 weeks since prior radiotherapy

    • Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy

    • Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration

    • ECOG (Eastern Cooperative Oncology Group) performance status 0-1

    • Leukocytes ≥ 3,000/mm^3

    • Absolute neutrophil count ≥ 1,500/mm^3

    • Platelet count ≥ 100,000/mm^3

    • Total bilirubin ≤ institutional upper limit of normal (ULN)

    • AST and ALT ≤ 3 times ULN

    • Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min

    • Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be <

    • Measurable or non-measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumours) criteria

    • Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet

    • Concurrent therapeutic anti-coagulation allowed

    • Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy

    Exclusion Criteria (Step 1 Induction Therapy):

    • Prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ

    • Prior systemic chemotherapy for advanced stage lung cancer

    • Prior use of paclitaxel, pemetrexed disodium, or bevacizumab

    • Major hemoptysis within the past 4 weeks

    • Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements

    • History of arterial thrombotic events or major bleeding within the past 12 months

    • Major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration. Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol.

    • Core biopsy within 7 days of registration

    • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months

    • Clinically significant cardiovascular disease

    • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

    • History of serious non-healing wounds, ulcers, or bone fractures

    • Cavitary lesions in the lungs

    • Pregnant or nursing

    • Concurrent anti-retroviral therapy in patients with HIV infection

    Inclusion Criteria (Step 2 Maintenance Therapy):

    • Patient must have an overall stable or better response after 4 courses of induction therapy

    • ECOG (Eastern Cooperative Oncology Group) performance status 0-1

    • Patients must be registered to Step 2 within 6 weeks of the last day of chemotherapy administration on Step 1

    • Acceptable bone marrow, renal and hepatic function within 2 weeks of registration

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Regional Medical Center Anniston Alabama United States 36207
    2 Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital Fairbanks Alaska United States 99701
    3 North Bay Cancer Center Fairfield California United States 94533
    4 Todd Cancer Institute at Long Beach Memorial Medical Center Long Beach California United States 90806
    5 Community Hospital of the Monterey Peninsula Comprehensive Cancer Center Monterey California United States 93940
    6 Veterans Affairs Medical Center - Palo Alto Palo Alto California United States 94304
    7 Feather River Hospital Cancer Center Paradise California United States 95969
    8 Sutter Cancer Center at Roseville Medical Center Roseville California United States 95661
    9 Sutter Cancer Center Sacramento California United States 95816
    10 Salinas Valley Memorial Hospital Salinas California United States 93901
    11 Stanford Cancer Center Stanford California United States 94305-5824
    12 Aurora Presbyterian Hospital Aurora Colorado United States 80012
    13 Boulder Community Hospital Boulder Colorado United States 80301-9019
    14 Penrose Cancer Center at Penrose Hospital Colorado Springs Colorado United States 80933
    15 St. Anthony Central Hospital Denver Colorado United States 80204
    16 Kaiser Permanente - Denver Denver Colorado United States 80205
    17 Porter Adventist Hospital Denver Colorado United States 80210
    18 Presbyterian - St. Luke's Medical Center Denver Colorado United States 80218
    19 St. Joseph Hospital Denver Colorado United States 80218
    20 Rose Medical Center Denver Colorado United States 80220
    21 CCOP - Colorado Cancer Research Program Denver Colorado United States 80222
    22 Swedish Medical Center Englewood Colorado United States 80110
    23 Poudre Valley Hospital Fort Collins Colorado United States 80524
    24 Front Range Cancer Specialists Fort Collins Colorado United States 80528
    25 North Colorado Medical Center Greeley Colorado United States 80631
    26 Kaiser Permanente - Lafayette Lafayette Colorado United States 80026
    27 Littleton Adventist Hospital Littleton Colorado United States 80122
    28 Sky Ridge Medical Center Lone Tree Colorado United States 80124
    29 Hope Cancer Care Center at Longmont United Hospital Longmont Colorado United States 80501
    30 McKee Medical Center Loveland Colorado United States 80539
    31 Parker Adventist Hospital Parker Colorado United States 80138
    32 St. Mary - Corwin Regional Medical Center Pueblo Colorado United States 81004
    33 North Suburban Medical Center Thornton Colorado United States 80229
    34 Exempla Lutheran Medical Center Wheat Ridge Colorado United States 80033
    35 Praxair Cancer Center at Danbury Hospital Danbury Connecticut United States 06810
    36 Helen and Harry Gray Cancer Center at Hartford Hospital Hartford Connecticut United States 06102-5037
    37 Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford Connecticut United States 06105
    38 George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus New Britain Connecticut United States 06050
    39 Kaiser Permanente at Capitol Hill Medical Center Washington District of Columbia United States 20002
    40 Sibley Memorial Hospital Washington District of Columbia United States 20016
    41 Veterans Affairs Medical Center - Washington, DC Washington District of Columbia United States 20422
    42 North Broward Medical Center Deerfield Beach Florida United States 33064-3596
    43 Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital Fort Lauderdale Florida United States 33308
    44 Broward General Medical Center Cancer Center Fort Lauderdale Florida United States 33316
    45 Memorial Cancer Institute at Memorial Regional Hospital Hollywood Florida United States 33021
    46 Ella Milbank Foshay Cancer Center at Jupiter Medical Center Jupiter Florida United States 33458
    47 CCOP - Mount Sinai Medical Center Miami Beach Florida United States 33140
    48 Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando Florida United States 32803-1273
    49 Sacred Heart Cancer Center at Sacred Heart Hospital Pensacola Florida United States 32504
    50 Sacred Heart Medical Oncology Pensacola Florida United States 32514
    51 Cleveland Clinic Florida - Weston Weston Florida United States 33331
    52 Phoebe Cancer Center at Phoebe Putney Memorial Hospital Albany Georgia United States 31701
    53 Winship Cancer Institute of Emory University Atlanta Georgia United States 30322
    54 Veterans Affairs Medical Center - Atlanta (Decatur) Decatur Georgia United States 30033
    55 Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler Savannah Georgia United States 31405
    56 Pearlman Comprehensive Cancer Center at South Georgia Medical Center Valdosta Georgia United States 31602
    57 Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise Idaho United States 83706
    58 Mountain States Tumor Institute at St. Luke's Regional Medical Center Boise Idaho United States 83712
    59 Saint Luke's Mountain States Tumor Institute - Fruitland Fruitland Idaho United States 83619
    60 St. Joseph Regional Medical Center Lewiston Idaho United States 83501
    61 Mountain States Tumor Institute - Meridian Meridian Idaho United States 83642
    62 Saint Luke's Mountain States Tumor Institute Nampa Idaho United States 83686
    63 Mountain States Tumor Institute at St. Luke's Twin Falls Idaho United States 83301
    64 Rush-Copley Cancer Care Center Aurora Illinois United States 60504
    65 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611-3013
    66 Hematology and Oncology Associates Chicago Illinois United States 60611
    67 University of Illinois Cancer Center Chicago Illinois United States 60612-7243
    68 Veterans Affairs Medical Center - Chicago Westside Hospital Chicago Illinois United States 60612
    69 Swedish Covenant Hospital Chicago Illinois United States 60625
    70 Resurrection Medical Center Chicago Illinois United States 60631
    71 Louis A. Weiss Memorial Hospital Chicago Illinois United States 60640
    72 Saint Joseph Hospital Chicago Illinois United States 60657
    73 Elmhurst Memorial Hospital Elmhurst Illinois United States 60126
    74 St. Francis Hospital Evanston Illinois United States 60202
    75 Leonard C. Ferguson Cancer Center Freeport Illinois United States 61032
    76 Delnor Hospital - Geneva Geneva Illinois United States 60134
    77 Kellogg Cancer Care Center Highland Park Illinois United States 60035
    78 Hinsdale Hematology Oncology Associates Hinsdale Illinois United States 60521
    79 Joliet Oncology-Hematology Associates, Limited - West Joliet Illinois United States 60435
    80 Provena St. Mary's Regional Cancer Center - Kankakee Kankakee Illinois United States 60901
    81 La Grange Memorial Hospital La Grange Illinois United States 60525
    82 North Shore Oncology and Hematology Associates, Limited - Libertyville Libertyville Illinois United States 60048
    83 Cancer Care and Hematology Specialists of Chicagoland - Niles Niles Illinois United States 60714
    84 West Suburban Center for Cancer Care River Forest Illinois United States 60305
    85 Swedish-American Regional Cancer Center Rockford Illinois United States 61104-2315
    86 Center for Cancer Care at OSF Saint Anthony Medical Center Rockford Illinois United States 61108
    87 Hematology Oncology Associates - Skokie Skokie Illinois United States 60076
    88 CCOP - Carle Cancer Center Urbana Illinois United States 61801
    89 Central Dupage Cancer Center Warrenville Illinois United States 60555
    90 St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove Indiana United States 46107
    91 Clarian Arnett Cancer Care Lafayette Indiana United States 47904
    92 Suniti Medical Corporation Merrillville Indiana United States 46410
    93 Saint Anthony Memorial Health Centers Michigan City Indiana United States 46360
    94 Reid Hospital & Health Care Services Richmond Indiana United States 47374
    95 McFarland Clinic, PC Ames Iowa United States 50010
    96 Hematology Oncology Associates of the Quad Cities Bettendorf Iowa United States 52722
    97 Iowa Blood and Cancer Care Cedar Rapids Iowa United States 52402
    98 St. Luke's Hospital Cedar Rapids Iowa United States 52402
    99 Cedar Rapids Oncology Associates Cedar Rapids Iowa United States 52403
    100 Mercy Regional Cancer Center at Mercy Medical Center Cedar Rapids Iowa United States 52403
    101 Medical Oncology and Hematology Associates - West Des Moines Clive Iowa United States 50325
    102 Mercy Cancer Center - West Lakes Clive Iowa United States 50325
    103 Heartland Oncology and Hematology Council Bluffs Iowa United States 51503
    104 CCOP - Iowa Oncology Research Association Des Moines Iowa United States 50309
    105 John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines Iowa United States 50309
    106 Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines Iowa United States 50309
    107 Medical Oncology and Hematology Associates at Mercy Cancer Center Des Moines Iowa United States 50314
    108 Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
    109 John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines Iowa United States 50316
    110 Mercy Cancer Center at Mercy Medical Center - North Iowa Mason City Iowa United States 50401
    111 McCreery Cancer Center at Ottumwa Regional Ottumwa Iowa United States 52501
    112 Siouxland Hematology-Oncology Associates, LLP Sioux City Iowa United States 51101
    113 Mercy Medical Center - Sioux City Sioux City Iowa United States 51102
    114 St. Luke's Regional Medical Center Sioux City Iowa United States 51104
    115 Covenant Cancer Treatment Center Waterloo Iowa United States 50702
    116 Methodist West Hospital West Des Moines Iowa United States 50266-7700
    117 Providence Medical Center Kansas City Kansas United States 66112
    118 Menorah Medical Center Overland Park Kansas United States 66209
    119 Saint Luke's Hospital - South Overland Park Kansas United States 66213
    120 CCOP - Kansas City Prairie Village Kansas United States 66208
    121 Mitchell Memorial Cancer Center at Owensboro Medical Health System Owensboro Kentucky United States 42303
    122 Mary Bird Perkins Cancer Center - Baton Rouge Baton Rouge Louisiana United States 70809
    123 Ochsner Health Center - Bluebonnet Baton Rouge Louisiana United States 70809
    124 Ochsner Health Center - Covington Covington Louisiana United States 70433
    125 Louisiana State University Health Sciences Center - Monroe Monroe Louisiana United States 71210
    126 MBCCOP - LSU Health Sciences Center New Orleans Louisiana United States 70112
    127 Medical Center of Louisiana - New Orleans New Orleans Louisiana United States 70112
    128 New Orleans Cancer Institute at Memorial Medical Center New Orleans Louisiana United States 70115
    129 CCOP - Ochsner New Orleans Louisiana United States 70121
    130 Ochsner Cancer Institute at Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    131 Feist-Weiller Cancer Center at Louisiana State University Health Sciences Shreveport Louisiana United States 71130-3932
    132 Harold Alfond Center for Cancer Care Augusta Maine United States 04330
    133 CancerCare of Maine at Eastern Maine Medical Center Bangor Maine United States 04401
    134 Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore Maryland United States 21215
    135 Kaiser Permanente at Woodlawn Medical Center Baltimore Maryland United States 21244
    136 Regional Cancer Center at Western Maryland Health System - Sacred Heart Campus Cumberland Maryland United States 21502
    137 Frederick Memorial Hospital Regional Cancer Therapy Center Frederick Maryland United States 21701
    138 Kaiser Permanente - Gaithersburg Medical Center Gaithersburg Maryland United States 20879
    139 Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility Largo Maryland United States 20774
    140 Peninsula Regional Medical Center Salisbury Maryland United States 21801
    141 Holy Cross Hospital Silver Spring Maryland United States 20910
    142 Sturdy Memorial Hospital Attleboro Massachusetts United States 02703
    143 Addison Gilbert Hospital Gloucester Massachusetts United States 01930
    144 Jordan Hospital Club Cancer Center Plymouth Massachusetts United States 02360
    145 Baystate Regional Cancer Program at D'Amour Center for Cancer Care Springfield Massachusetts United States 01199
    146 UMASS Memorial Cancer Center - University Campus Worcester Massachusetts United States 01655
    147 Hickman Cancer Center at Bixby Medical Center Adrian Michigan United States 49221
    148 Saint Joseph Mercy Cancer Center Ann Arbor Michigan United States 48106-0995
    149 CCOP - Michigan Cancer Research Consortium Ann Arbor Michigan United States 48106
    150 Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn Michigan United States 48123-2500
    151 Green Bay Oncology, Limited - Escanaba Escanaba Michigan United States 49431
    152 Genesys Hurley Cancer Institute Flint Michigan United States 48503
    153 Hurley Medical Center Flint Michigan United States 48503
    154 Genesys Regional Medical Center Grand Blanc Michigan United States 48439
    155 Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods Michigan United States 48236
    156 Dickinson County Healthcare System Iron Mountain Michigan United States 49801
    157 Foote Memorial Hospital Jackson Michigan United States 49201
    158 Borgess Medical Center Kalamazoo Michigan United States 49001
    159 West Michigan Cancer Center Kalamazoo Michigan United States 49007-3731
    160 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    161 Sparrow Regional Cancer Center Lansing Michigan United States 48912-1811
    162 St. Mary Mercy Hospital Livonia Michigan United States 48154
    163 Upper Michigan Cancer Center at Marquette General Hospital Marquette Michigan United States 49855
    164 Community Cancer Center of Monroe Monroe Michigan United States 48162
    165 Mercy Memorial Hospital - Monroe Monroe Michigan United States 48162
    166 St. Joseph Mercy Oakland Pontiac Michigan United States 48341-2985
    167 Mercy Regional Cancer Center at Mercy Hospital Port Huron Michigan United States 48060
    168 Seton Cancer Institute at Saint Mary's - Saginaw Saginaw Michigan United States 48601
    169 St. John Macomb Hospital Warren Michigan United States 48093
    170 MeritCare Bemidji Bemidji Minnesota United States 56601
    171 St. Joseph's Medical Center Brainerd Minnesota United States 56401
    172 Fairview Ridges Hospital Burnsville Minnesota United States 55337
    173 Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids Minnesota United States 55433
    174 Duluth Clinic Cancer Center - Duluth Duluth Minnesota United States 55805-1983
    175 CCOP - Duluth Duluth Minnesota United States 55805
    176 Miller - Dwan Medical Center Duluth Minnesota United States 55805
    177 Fairview Southdale Hospital Edina Minnesota United States 55435
    178 Mercy and Unity Cancer Center at Unity Hospital Fridley Minnesota United States 55432
    179 Hutchinson Area Health Care Hutchinson Minnesota United States 55350
    180 Immanuel St. Joseph's Mankato Minnesota United States 56002
    181 HealthEast Cancer Care at St. John's Hospital Maplewood Minnesota United States 55109
    182 Minnesota Oncology - Maplewood Maplewood Minnesota United States 55109
    183 Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis Minnesota United States 55407
    184 Hennepin County Medical Center - Minneapolis Minneapolis Minnesota United States 55415
    185 New Ulm Medical Center New Ulm Minnesota United States 56073
    186 Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale Minnesota United States 55422-2900
    187 CCOP - Metro-Minnesota Saint Louis Park Minnesota United States 55416
    188 Park Nicollet Cancer Center Saint Louis Park Minnesota United States 55416
    189 Regions Hospital Cancer Care Center Saint Paul Minnesota United States 55101
    190 United Hospital Saint Paul Minnesota United States 55102
    191 St. Francis Cancer Center at St. Francis Medical Center Shakopee Minnesota United States 55379
    192 Lakeview Hospital Stillwater Minnesota United States 55082
    193 Ridgeview Medical Center Waconia Minnesota United States 55387
    194 Willmar Cancer Center at Rice Memorial Hospital Willmar Minnesota United States 56201
    195 Minnesota Oncology - Woodbury Woodbury Minnesota United States 55125
    196 Regional Cancer Center at Singing River Hospital Pascagoula Mississippi United States 39581
    197 Central Care Cancer Center at Carrie J. Babb Cancer Center Bolivar Missouri United States 65613
    198 Skaggs Cancer Center at Skaggs Regional Medical Center Branson Missouri United States 65616
    199 Southeast Cancer Center Cape Girardeau Missouri United States 63703
    200 Goldschmidt Cancer Center Jefferson City Missouri United States 65109
    201 St. John's Regional Medical Center Joplin Missouri United States 64804
    202 Saint Luke's Cancer Institute at Saint Luke's Hospital Kansas City Missouri United States 64111
    203 North Kansas City Hospital Kansas City Missouri United States 64116
    204 Heartland Hematology Oncology Associates, Incorporated Kansas City Missouri United States 64118
    205 Research Medical Center Kansas City Missouri United States 64132
    206 Saint Luke's East - Lee's Summit Lee's Summit Missouri United States 64086
    207 Parvin Radiation Oncology Liberty Missouri United States 64068
    208 Mercy Clinic Cancer and Hematology - Rolla Rolla Missouri United States 65401
    209 Phelps County Regional Medical Center Rolla Missouri United States 65401
    210 Heartland Regional Medical Center Saint Joseph Missouri United States 64506
    211 Saint Joseph Oncology, Incorporated Saint Joseph Missouri United States 64507
    212 St. Anthony's Cancer Center Saint Louis Missouri United States 63128
    213 Missouri Baptist Cancer Center Saint Louis Missouri United States 63131
    214 CCOP - Cancer Research for the Ozarks Springfield Missouri United States 65802
    215 St. John's Regional Health Center Springfield Missouri United States 65804
    216 Hulston Cancer Center at Cox Medical Center South Springfield Missouri United States 65807
    217 CCOP - Montana Cancer Consortium Billings Montana United States 59101
    218 St. Vincent Healthcare Cancer Care Services Billings Montana United States 59101
    219 Hematology-Oncology Centers of the Northern Rockies - Billings Billings Montana United States 59102
    220 Billings Clinic - Downtown Billings Montana United States 59107-7000
    221 Bozeman Deaconess Cancer Center Bozeman Montana United States 59715
    222 St. James Healthcare Cancer Care Butte Montana United States 59701
    223 Great Falls Clinic - Main Facility Great Falls Montana United States 59405
    224 Sletten Cancer Institute at Benefis Healthcare Great Falls Montana United States 59405
    225 St. Peter's Hospital Helena Montana United States 59601
    226 Glacier Oncology, PLLC Kalispell Montana United States 59901
    227 Kalispell Medical Oncology at KRMC Kalispell Montana United States 59901
    228 Kalispell Regional Medical Center Kalispell Montana United States 59901
    229 Montana Cancer Specialists at Montana Cancer Center Missoula Montana United States 59807-7877
    230 Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula Montana United States 59807
    231 Good Samaritan Cancer Center at Good Samaritan Hospital Kearney Nebraska United States 68848-1990
    232 Cancer Resource Center - Lincoln Lincoln Nebraska United States 68510
    233 CCOP - Missouri Valley Cancer Consortium Omaha Nebraska United States 68106
    234 Immanuel Medical Center Omaha Nebraska United States 68122
    235 Alegant Health Cancer Center at Bergan Mercy Medical Center Omaha Nebraska United States 68124
    236 Lakeside Hospital Omaha Nebraska United States 68130
    237 Creighton University Medical Center Omaha Nebraska United States 68131-2197
    238 Renown Institute for Cancer at Renown Regional Medical Center Reno Nevada United States 89502
    239 Seacoast Cancer Center at Wentworth - Douglass Hospital Dover New Hampshire United States 03820
    240 Oncology Center at St. Joseph Hospital Nashua New Hampshire United States 03060
    241 Veterans Affairs Medical Center - East Orange East Orange New Jersey United States 07018-1095
    242 Monmouth Medical Center Long Branch New Jersey United States 07740-6395
    243 Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton Marlton New Jersey United States 08053
    244 Carol G. Simon Cancer Center at Morristown Memorial Hospital Morristown New Jersey United States 07960
    245 UMDNJ University Hospital Newark New Jersey United States 07103
    246 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    247 Frederick R. and Betty M. Smith Cancer Treatment Center Sparta New Jersey United States 07871
    248 Overlook Hospital Summit New Jersey United States 07901
    249 Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare Vineland New Jersey United States 08360
    250 Fox Chase Virtua Health Cancer Program at Virtua West Jersey Voorhees New Jersey United States 08043
    251 Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx New York United States 10461
    252 Maimonides Cancer Center at Maimonides Medical Center Brooklyn New York United States 11219
    253 Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital Cooperstown New York United States 13326
    254 Charles R. Wood Cancer Center at Glens Falls Hospital Glens Falls New York United States 12801
    255 Nalitt Cancer Institute at Staten Island University Hospital Staten Island New York United States 10305
    256 Stony Brook University Cancer Center Stony Brook New York United States 11794-9446
    257 Faxton Regional Cancer Center Utica New York United States 13502
    258 Dickstein Cancer Treatment Center at White Plains Hospital Center White Plains New York United States 10601
    259 Randolph Hospital Asheboro North Carolina United States 27203-5400
    260 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill North Carolina United States 27599-7295
    261 Presbyterian Cancer Center at Presbyterian Hospital Charlotte North Carolina United States 28233-3549
    262 Wayne Memorial Hospital, Incorporated Goldsboro North Carolina United States 27534
    263 Moses Cone Regional Cancer Center at Wesley Long Community Hospital Greensboro North Carolina United States 27403-1198
    264 Pardee Memorial Hospital Hendersonville North Carolina United States 28791
    265 Kinston Medical Specialists Kinston North Carolina United States 28501
    266 Annie Penn Cancer Center Reidsville North Carolina United States 27320
    267 Rutherford Hospital Rutherfordton North Carolina United States 28139
    268 Iredell Memorial Hospital Statesville North Carolina United States 28677
    269 Medcenter One Hospital Cancer Care Center Bismarck North Dakota United States 58501
    270 Mid Dakota Clinic, PC Bismarck North Dakota United States 58501
    271 St. Alexius Medical Center Cancer Center Bismarck North Dakota United States 58502
    272 MeritCare Broadway Fargo North Dakota United States 58102
    273 Dakota Cancer Institute at Dakota Clinic - South University Fargo North Dakota United States 58103
    274 CCOP - MeritCare Hospital Fargo North Dakota United States 58122
    275 Roger Maris Cancer Center at MeritCare Hospital Fargo North Dakota United States 58122
    276 Altru Cancer Center at Altru Hospital Grand Forks North Dakota United States 58201
    277 Trinity CancerCare Center Minot North Dakota United States 58701
    278 Cleveland Clinic Beachwood Family Health and Surgery Center Beachwood Ohio United States 44122
    279 Wood County Oncology Center Bowling Green Ohio United States 43402
    280 Mercy Cancer Center at Mercy Medical Center Canton Ohio United States 44708
    281 Aultman Cancer Center at Aultman Hospital Canton Ohio United States 44710-1799
    282 Case Comprehensive Cancer Center Cleveland Ohio United States 44106-5065
    283 MetroHealth Cancer Care Center at MetroHealth Medical Center Cleveland Ohio United States 44109
    284 Cleveland Clinic Cancer Center at Fairview Hospital Cleveland Ohio United States 44111
    285 Cleveland Clinic Taussig Cancer Center Cleveland Ohio United States 44195
    286 Grandview Hospital Dayton Ohio United States 45405
    287 Good Samaritan Hospital Dayton Ohio United States 45406
    288 David L. Rike Cancer Center at Miami Valley Hospital Dayton Ohio United States 45409
    289 Samaritan North Cancer Care Center Dayton Ohio United States 45415
    290 CCOP - Dayton Dayton Ohio United States 45420
    291 Community Cancer Center Elyria Ohio United States 44035
    292 Hematology Oncology Center Elyria Ohio United States 44035
    293 Blanchard Valley Medical Associates Findlay Ohio United States 45840
    294 Middletown Regional Hospital Franklin Ohio United States 45005-1066
    295 Wayne Hospital Greenville Ohio United States 45331
    296 Cleveland Clinic Cancer Center Independence Ohio United States 44131
    297 Charles F. Kettering Memorial Hospital Kettering Ohio United States 45429
    298 St. Rita's Medical Center Lima Ohio United States 45801
    299 Lima Memorial Hospital Lima Ohio United States 45804
    300 Northwest Ohio Oncology Center Maumee Ohio United States 43537-1839
    301 Hillcrest Cancer Center at Hillcrest Hospital Mayfield Heights Ohio United States 44124
    302 Southwest General Health Center Middleburg Heights Ohio United States 44130
    303 UHHS Chagrin Highlands Medical Center Orange Village Ohio United States 44122
    304 St. Charles Mercy Hospital Oregon Ohio United States 43616
    305 Toledo Clinic - Oregon Oregon Ohio United States 43616
    306 Parma Community General Hospital Parma Ohio United States 44129
    307 North Coast Cancer Care, Incorporated Sandusky Ohio United States 44870
    308 Cleveland Clinic Foundation - Strongsville Strongsville Ohio United States 44136
    309 Flower Hospital Cancer Center Sylvania Ohio United States 43560
    310 Mercy Hospital of Tiffin Tiffin Ohio United States 44883
    311 Toledo Hospital Toledo Ohio United States 43606
    312 St. Vincent Mercy Medical Center Toledo Ohio United States 43608
    313 Medical University of Ohio Cancer Center Toledo Ohio United States 43614
    314 CCOP - Toledo Community Hospital Toledo Ohio United States 43617
    315 St. Anne Mercy Hospital Toledo Ohio United States 43623
    316 Toledo Clinic, Incorporated - Main Clinic Toledo Ohio United States 43623
    317 UVMC Cancer Care Center at Upper Valley Medical Center Troy Ohio United States 45373-1300
    318 Fulton County Health Center Wauseon Ohio United States 43567
    319 UHHS Westlake Medical Center Westlake Ohio United States 44145
    320 Cleveland Clinic - Wooster Wooster Ohio United States 44691
    321 United States Air Force Medical Center - Wright-Patterson Wright-Patterson Air Force Base Ohio United States 45433-5529
    322 Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia Ohio United States 45385
    323 Cancer Care Associates - Norman Norman Oklahoma United States 73071
    324 Cancer Care Associates - Mercy Campus Oklahoma City Oklahoma United States 73120
    325 Natalie Warren Bryant Cancer Center at St. Francis Hospital Tulsa Oklahoma United States 74136
    326 Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Allentown Pennsylvania United States 18105
    327 Bryn Mawr Hospital Bryn Mawr Pennsylvania United States 19010
    328 Geisinger Cancer Institute at Geisinger Health Danville Pennsylvania United States 17822-0001
    329 Mercy Fitzgerald Hospital Darby Pennsylvania United States 19023
    330 Ephrata Cancer Center at Ephrata Community Hospital Ephrata Pennsylvania United States 17522
    331 Regional Cancer Center - Erie Erie Pennsylvania United States 16505
    332 Fox Chase Cancer Center Buckingham Furlong Pennsylvania United States 18925
    333 Adams Cancer Center Gettysburg Pennsylvania United States 17325
    334 Cherry Tree Cancer Center Hanover Pennsylvania United States 17331
    335 PinnacleHealth Regional Cancer Center at Polyclinic Hospital Harrisburg Pennsylvania United States 17110-2098
    336 Geisinger Hazleton Cancer Center Hazleton Pennsylvania United States 18201
    337 Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033-0850
    338 Lancaster General Hospital Lancaster Pennsylvania United States 17604
    339 Lewistown Hospital Lewistown Pennsylvania United States 17044
    340 Riddle Memorial Hospital Cancer Center Media Pennsylvania United States 19063
    341 Cancer Center of Paoli Memorial Hospital Paoli Pennsylvania United States 19301-1792
    342 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia Pennsylvania United States 19107-5541
    343 Fox Chase Cancer Center - Philadelphia Philadelphia Pennsylvania United States 19111-2497
    344 Frankford Hospital Cancer Center - Torresdale Campus Philadelphia Pennsylvania United States 19114
    345 Albert Einstein Cancer Center Philadelphia Pennsylvania United States 19141
    346 Iris V. Henderson Cancer Center at Mercy Hospital of Philadelphia Philadelphia Pennsylvania United States 19143
    347 St. Joseph Medical Center Reading Pennsylvania United States 19605
    348 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center Reading Pennsylvania United States 19612-6052
    349 Guthrie Cancer Center at Guthrie Clinic Sayre Sayre Pennsylvania United States 18840
    350 Mercy Hospital Cancer Center - Scranton Scranton Pennsylvania United States 18501
    351 Hematology and Oncology Associates of Northeastern Pennsylvania Scranton Pennsylvania United States 18510
    352 Grand View Hospital Sellersville Pennsylvania United States 18960
    353 Geisinger Medical Group - Scenery Park State College Pennsylvania United States 16801
    354 Mount Nittany Medical Center State College Pennsylvania United States 16803
    355 Chester County Hospital West Chester Pennsylvania United States 19380
    356 Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre Pennsylvania United States 18711
    357 Susquehanna Cancer Center at Divine Providence Hospital Williamsport Pennsylvania United States 17701
    358 CCOP - Main Line Health Wynnewood Pennsylvania United States 19096
    359 Lankenau Cancer Center at Lankenau Hospital Wynnewood Pennsylvania United States 19096
    360 York Cancer Center at Apple Hill Medical Center York Pennsylvania United States 17405
    361 AnMed Cancer Center Anderson South Carolina United States 29621
    362 Cancer Centers of the Carolinas - Easley Easley South Carolina United States 29640
    363 Bon Secours St. Francis Health System Greenville South Carolina United States 29601
    364 Cancer Centers of the Carolinas - Faris Road Greenville South Carolina United States 29605
    365 Cancer Centers of the Carolinas - Grove Commons Greenville South Carolina United States 29605
    366 Greenville Hospital Cancer Center Greenville South Carolina United States 29605
    367 CCOP - Greenville Greenville South Carolina United States 29615
    368 Cancer Centers of the Carolinas - Greer Medical Oncology Greer South Carolina United States 29650
    369 Cancer Centers of the Carolinas - Seneca Seneca South Carolina United States 29672
    370 CCOP - Upstate Carolina Spartanburg South Carolina United States 29303
    371 Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg South Carolina United States 29303
    372 Cancer Centers of the Carolinas - Spartanburg Spartanburg South Carolina United States 29307
    373 Oncology Services of Aberdeen Aberdeen South Dakota United States 57401
    374 Rapid City Regional Hospital Rapid City South Dakota United States 57701
    375 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    376 Sanford Cancer Center at Sanford USD Medical Center Sioux Falls South Dakota United States 57117-5039
    377 West Tennessee Cancer Center at Jackson-Madison County General Hospital Jackson Tennessee United States 38301
    378 Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center Kingsport Tennessee United States 37662
    379 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232-6838
    380 Hendrick Cancer Center Abilene Texas United States 79601
    381 Harrington Cancer Center Amarillo Texas United States 79106
    382 M. D. Anderson Cancer Center at University of Texas Houston Texas United States 77030-4009
    383 Community Cancer Center at Rutland Regional Medical Center Rutland Vermont United States 05701
    384 Fredericksburg Oncology, Incorporated Fredericksburg Virginia United States 22401
    385 Virginia Oncology Associates - Hampton Hampton Virginia United States 23666
    386 Kaiser Permanente Tysons Corner Medical Center McLean Virginia United States 22102
    387 Southwest Virginia Regional Cancer Center at Wellmonth Health Norton Virginia United States 24273
    388 Virginia Commonwealth University Massey Cancer Center Richmond Virginia United States 23298-0037
    389 Auburn Regional Center for Cancer Care Auburn Washington United States 98002
    390 Overlake Cancer Center at Overlake Hospital Medical Center Bellevue Washington United States 98004
    391 Providence Centralia Hospital Centralia Washington United States 98531-9027
    392 Providence Regional Cancer Partnership Everett Washington United States 98201
    393 St. Francis Hospital Federal Way Washington United States 98003
    394 Cascade Cancer Center at Evergreen Hospital Medical Center Kirkland Washington United States 98033
    395 Providence St. Peter Hospital Regional Cancer Center Olympia Washington United States 98506-5166
    396 Good Samaritan Cancer Center Puyallup Washington United States 98372
    397 CCOP - Virginia Mason Research Center Seattle Washington United States 98101
    398 Virginia Mason Medical Center Seattle Washington United States 98101
    399 Pacific Medical Center Seattle Washington United States 98104
    400 Rockwood Clinic Cancer Treatment Center Spokane Washington United States 99204-2967
    401 Franciscan Cancer Center at St. Joseph Medical Center Tacoma Washington United States 98405-3004
    402 Allenmore Hospital Tacoma Washington United States 98405
    403 CCOP - Northwest Tacoma Washington United States 98405
    404 MultiCare Regional Cancer Center at Tacoma General Hospital Tacoma Washington United States 98405
    405 St. Clare Hospital Tacoma Washington United States 98499
    406 West Virginia University Health Sciences Center - Charleston Charleston West Virginia United States 25304
    407 Mary Babb Randolph Cancer Center at West Virginia University Hospitals Morgantown West Virginia United States 26506
    408 Langlade Memorial Hospital Antigo Wisconsin United States 54409
    409 Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin United States 54301-3526
    410 Bellin Memorial Hospital Green Bay Wisconsin United States 54301
    411 Green Bay Oncology, Limited at St. Mary's Hospital Green Bay Wisconsin United States 54303
    412 St. Mary's Hospital Medical Center - Green Bay Green Bay Wisconsin United States 54303
    413 St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin United States 54307-3508
    414 Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center Green Bay Wisconsin United States 54311
    415 Mercy Regional Cancer Center Janesville Wisconsin United States 53547
    416 Gundersen Lutheran Center for Cancer and Blood La Crosse Wisconsin United States 54601
    417 Holy Family Memorial Medical Center Cancer Care Center Manitowoc Wisconsin United States 54221-1450
    418 Bay Area Cancer Care Center at Bay Area Medical Center Marinette Wisconsin United States 54143
    419 Vince Lombardi Cancer Clinic - Marinette Marinette Wisconsin United States 54143
    420 Wheaton Franciscan Cancer Care - St. Joseph Milwaukee Wisconsin United States 53210
    421 D.N. Greenwald Center Mukwonago Wisconsin United States 53149
    422 Regional Cancer Center at Oconomowoc Memorial Hospital Oconomowoc Wisconsin United States 53066
    423 Green Bay Oncology, Limited - Oconto Falls Oconto Falls Wisconsin United States 54154
    424 Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin United States 54904
    425 St. Nicholas Hospital Sheboygan Wisconsin United States 53081
    426 Vince Lombardi Cancer Clinic - Sheboygan Sheboygan Wisconsin United States 53081
    427 Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay Wisconsin United States 54235
    428 Aurora Medical Center Summit Wisconsin United States 53066
    429 Vince Lombardi Cancer Clinic - Two Rivers Two Rivers Wisconsin United States 54241
    430 Waukesha Memorial Hospital Regional Cancer Center Waukesha Wisconsin United States 53188
    431 University of Wisconcin Cancer Center at Aspirus Wausau Hospital Wausau Wisconsin United States 54401
    432 Oncology Alliance, SC - Milwaukee - West Wauwatosa Wisconsin United States 53226
    433 Riverview UW Cancer Center at Riverview Hospital Wisconsin Rapids Wisconsin United States 54494
    434 Rocky Mountain Oncology Casper Wyoming United States 82609

    Sponsors and Collaborators

    • ECOG-ACRIN Cancer Research Group
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Suresh Ramalingam, MD, Emory University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    ECOG-ACRIN Cancer Research Group
    ClinicalTrials.gov Identifier:
    NCT01107626
    Other Study ID Numbers:
    • E5508
    First Posted:
    Apr 21, 2010
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by ECOG-ACRIN Cancer Research Group
    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
    Paclitaxel
    Bevacizumab
    Carboplatin
    Pemetrexed

    Study Results

    Participant Flow

    Recruitment Details A total of 1,516 patients were enrolled in the study between August 2010 and April 2015.
    Pre-assignment Detail
    Arm/Group Title Induction Therapy But Not Randomized to Maintenance Therapy Arm A (Induction Then Maintenance With Bevacizumab) Arm B (Induction Then Maintenance With Pemetrexed Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.
    Period Title: Step 1: Induction Therapy
    STARTED 642 287 294 293
    COMPLETED 65 287 294 293
    NOT COMPLETED 577 0 0 0
    Period Title: Step 1: Induction Therapy
    STARTED 0 287 294 293
    COMPLETED 0 1 0 1
    NOT COMPLETED 0 286 294 292

    Baseline Characteristics

    Arm/Group Title Induction Therapy But Not Randomized Arm A (Induction Then Maintenance With Bevacizumab) Arm B (Induction Then Maintenance With Pemetrexed) Arm C (Inductio Then Maintenance With Bevacizumab & Pemetrexed) Total
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 642 287 294 293 1516
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    65
    65
    63
    64
    64
    Sex: Female, Male (Count of Participants)
    Female
    276
    43%
    147
    51.2%
    151
    51.4%
    150
    51.2%
    724
    47.8%
    Male
    366
    57%
    140
    48.8%
    143
    48.6%
    143
    48.8%
    792
    52.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    6
    0.9%
    1
    0.3%
    1
    0.3%
    1
    0.3%
    9
    0.6%
    Asian
    8
    1.2%
    3
    1%
    3
    1%
    6
    2%
    20
    1.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.3%
    1
    0.3%
    0
    0%
    2
    0.1%
    Black or African American
    82
    12.8%
    31
    10.8%
    45
    15.3%
    22
    7.5%
    180
    11.9%
    White
    528
    82.2%
    245
    85.4%
    240
    81.6%
    260
    88.7%
    1273
    84%
    More than one race
    0
    0%
    1
    0.3%
    0
    0%
    0
    0%
    1
    0.1%
    Unknown or Not Reported
    18
    2.8%
    5
    1.7%
    4
    1.4%
    4
    1.4%
    31
    2%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description Overall survival is defined as the time from randomization to death or date last known alive. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.
    Time Frame Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    All randomized patients
    Arm/Group Title Arm A (Induction Then Maintenance With Bevacizumab) Arm B (Induction Then Maintenance With Pemetrexed Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.
    Measure Participants 287 294 293
    Median (97.5% Confidence Interval) [months]
    14.4
    15.9
    16.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Induction Then Maintenance With Bevacizumab), Arm B (Induction Then Maintenance With Pemetrexed
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.12
    Comments
    Method Log Rank
    Comments Stratified logrank test
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm A (Induction Then Maintenance With Bevacizumab), Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.28
    Comments
    Method Log Rank
    Comments Stratified logrank test
    2. Secondary Outcome
    Title Progression-free Survival
    Description Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is evaluated based on RECIST criteria and defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on current step. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.
    Time Frame Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    All randomized patients
    Arm/Group Title Arm A (Induction Then Maintenance With Bevacizumab) Arm B (Induction Then Maintenance With Pemetrexed Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.
    Measure Participants 287 294 293
    Median (97.5% Confidence Interval) [months]
    4.2
    5.1
    7.5
    3. Secondary Outcome
    Title Response Rate
    Description Response is evaluated based on RECIST criteria v1.1 and defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the current step's baseline sum diameters. The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis.
    Time Frame Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    All randomized patients
    Arm/Group Title Arm A (Induction Then Maintenance With Bevacizumab) Arm B (Induction Then Maintenance With Pemetrexed Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.
    Measure Participants 287 294 293
    Number (97.5% Confidence Interval) [proportion of participants]
    0.125
    0%
    0.187
    0.1%
    0.212
    0.1%
    4. Other Pre-specified Outcome
    Title The Association Between Genotypes and Response Rate
    Description To determine the frequency of polymorphisms in VEGF 3578 AA, 1154 AA, ABCB1 G2677TT/AA and ERCC-118 TT in patients with NSCLC receiving paclitaxel, carboplatin and bevacizumab therapy and determine the association between genotypes and response rate.
    Time Frame Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Other Pre-specified Outcome
    Title The Association Between Bevacizumab and Pemetrexed Population Pharmacokinetics and Patient Specific Covariates With Bevacizumab or Pemetrexed Toxicity
    Description
    Time Frame Assessed every 3 weeks while on treatment and for 30 days after the end of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Other Pre-specified Outcome
    Title The Frequency of TSER*3 Polymorphisms in NSCLC and the Association Between TSER Polymorphisms and Benefit From Pemetrexed
    Description
    Time Frame Assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Other Pre-specified Outcome
    Title The Association Between TS and ERCC1 Expression and Pemetrexed Response
    Description
    Time Frame Assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    Title The Associations Between Polymorphisms Within CYPs 2C8, 3A4, 3A5 and/or the UGT1A1 Collectively or Monogenically and Efficacy and/or Toxicities
    Description
    Time Frame Assessed every 3 months for 2 years and every 6 months for years 3-5

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years
    Adverse Event Reporting Description Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
    Arm/Group Title Arm I (Induction Therapy - Carboplatin, Paclitaxel & Bevacizumab) Arm A (Maintenance Therapy - Bevacizumab) Arm B (Maintenance Therapy - Pemetrexed) Arm C (Maintenance Therapy - Bevacizumab + Pemetrexed)
    Arm/Group Description Induction Therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm A receive bevacizumab IV over 30-90 minutes on day 1 of every cycle until progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm B receive pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity. Maintenance Therapy: Patients achieving complete response, partial response or stable disease following induction therapy are randomized to 1 of 3 treatment arms. Patients in arm C receive bevacizumab IV over 30-90 minutes and pemetrexed IV over 10 minutes on day 1 of every cycle until progression or unacceptable toxicity.
    All Cause Mortality
    Arm I (Induction Therapy - Carboplatin, Paclitaxel & Bevacizumab) Arm A (Maintenance Therapy - Bevacizumab) Arm B (Maintenance Therapy - Pemetrexed) Arm C (Maintenance Therapy - Bevacizumab + Pemetrexed)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1290/1516 (85.1%) 245/287 (85.4%) 240/294 (81.6%) 236/293 (80.5%)
    Serious Adverse Events
    Arm I (Induction Therapy - Carboplatin, Paclitaxel & Bevacizumab) Arm A (Maintenance Therapy - Bevacizumab) Arm B (Maintenance Therapy - Pemetrexed) Arm C (Maintenance Therapy - Bevacizumab + Pemetrexed)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 825/1477 (55.9%) 87/284 (30.6%) 107/289 (37%) 144/286 (50.3%)
    Blood and lymphatic system disorders
    Anemia 91/1477 (6.2%) 6/284 (2.1%) 20/289 (6.9%) 19/286 (6.6%)
    Febrile neutropenia 52/1477 (3.5%) 0/284 (0%) 1/289 (0.3%) 4/286 (1.4%)
    Cardiac disorders
    Acute coronary syndrome 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Asystole 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Atrial fibrillation 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Cardiac arrest 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Chest pain - cardiac 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Heart failure 2/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Left ventricular systolic dysfunction 1/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Myocardial infarction 4/1477 (0.3%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Pericardial effusion 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Sinus tachycardia 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Cardiac disorders - Other, specify 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Eye disorders
    Eye disorders - Other, specify 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Abdominal pain 6/1477 (0.4%) 0/284 (0%) 0/289 (0%) 3/286 (1%)
    Ascites 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Colitis 7/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Colonic hemorrhage 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Colonic perforation 8/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Constipation 7/1477 (0.5%) 1/284 (0.4%) 0/289 (0%) 1/286 (0.3%)
    Diarrhea 32/1477 (2.2%) 0/284 (0%) 5/289 (1.7%) 5/286 (1.7%)
    Duodenal perforation 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Duodenal ulcer 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Dysphagia 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Esophageal fistula 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Esophageal perforation 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Esophagitis 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Gastric hemorrhage 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Gastric perforation 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 1/286 (0.3%)
    Gastric ulcer 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Gastritis 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Gastrointestinal pain 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Lower gastrointestinal hemorrhage 1/1477 (0.1%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Mucositis oral 15/1477 (1%) 0/284 (0%) 4/289 (1.4%) 1/286 (0.3%)
    Nausea 58/1477 (3.9%) 1/284 (0.4%) 2/289 (0.7%) 7/286 (2.4%)
    Obstruction gastric 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Pancreatitis 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Proctitis 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Rectal fistula 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Small intestinal obstruction 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Small intestinal perforation 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Stomach pain 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Upper gastrointestinal hemorrhage 1/1477 (0.1%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Vomiting 37/1477 (2.5%) 1/284 (0.4%) 1/289 (0.3%) 6/286 (2.1%)
    Gastrointestinal disorders - Other 1/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    General disorders
    Chills 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Death NOS 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Edema face 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Edema limbs 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Facial pain 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Fatigue 116/1477 (7.9%) 8/284 (2.8%) 22/289 (7.6%) 24/286 (8.4%)
    Fever 6/1477 (0.4%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Flu like symptoms 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Gait disturbance 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Hypothermia 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Infusion related reaction 8/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Infusion site extravasation 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Non-cardiac chest pain 4/1477 (0.3%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Pain 3/1477 (0.2%) 1/284 (0.4%) 0/289 (0%) 1/286 (0.3%)
    Sudden death NOS 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    General and administration site - Other 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Hepatobiliary disorders
    Hepatic failure 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Portal vein thrombosis 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Immune system disorders
    Allergic reaction 6/1477 (0.4%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Anaphylaxis 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Infections and infestations
    Abdominal infection 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Anorectal infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Catheter related infection 2/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Device related infection 4/1477 (0.3%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Duodenal infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Enterocolitis infectious 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Esophageal infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Lung infection 24/1477 (1.6%) 1/284 (0.4%) 6/289 (2.1%) 6/286 (2.1%)
    Lymph gland infection 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Mucosal infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Pelvic infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Sepsis 14/1477 (0.9%) 1/284 (0.4%) 0/289 (0%) 3/286 (1%)
    Skin infection 2/1477 (0.1%) 0/284 (0%) 3/289 (1%) 1/286 (0.3%)
    Small intestine infection 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Soft tissue infection 0/1477 (0%) 0/284 (0%) 0/289 (0%) 2/286 (0.7%)
    Upper respiratory infection 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Urinary tract infection 5/1477 (0.3%) 0/284 (0%) 2/289 (0.7%) 3/286 (1%)
    Infections and infestations - Other 4/1477 (0.3%) 0/284 (0%) 2/289 (0.7%) 0/286 (0%)
    Injury, poisoning and procedural complications
    Fall 1/1477 (0.1%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Hip fracture 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Vascular access complication 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Wound complication 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Wound dehiscence 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Investigations
    Alanine aminotransferase increased 3/1477 (0.2%) 1/284 (0.4%) 1/289 (0.3%) 0/286 (0%)
    Alkaline phosphatase increased 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Aspartate aminotransferase increased 4/1477 (0.3%) 0/284 (0%) 2/289 (0.7%) 2/286 (0.7%)
    Blood bilirubin increased 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Cardiac troponin I increased 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Cardiac troponin T increased 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    CD4 lymphocytes decreased 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Creatinine increased 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 4/286 (1.4%)
    Ejection fraction decreased 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    INR increased 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Lymphocyte count decreased 64/1477 (4.3%) 3/284 (1.1%) 16/289 (5.5%) 23/286 (8%)
    Neutrophil count decreased 403/1477 (27.3%) 3/284 (1.1%) 23/289 (8%) 32/286 (11.2%)
    Platelet count decreased 109/1477 (7.4%) 0/284 (0%) 11/289 (3.8%) 12/286 (4.2%)
    Weight gain 1/1477 (0.1%) 0/284 (0%) 2/289 (0.7%) 0/286 (0%)
    Weight loss 4/1477 (0.3%) 1/284 (0.4%) 1/289 (0.3%) 7/286 (2.4%)
    White blood cell decreased 213/1477 (14.4%) 0/284 (0%) 15/289 (5.2%) 14/286 (4.9%)
    Investigations - Other, specify 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Metabolism and nutrition disorders
    Anorexia 48/1477 (3.2%) 2/284 (0.7%) 5/289 (1.7%) 3/286 (1%)
    Dehydration 42/1477 (2.8%) 1/284 (0.4%) 5/289 (1.7%) 8/286 (2.8%)
    Hyperglycemia 16/1477 (1.1%) 0/284 (0%) 1/289 (0.3%) 2/286 (0.7%)
    Hyperkalemia 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Hypermagnesemia 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Hypoalbuminemia 8/1477 (0.5%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Hypocalcemia 5/1477 (0.3%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Hypokalemia 16/1477 (1.1%) 2/284 (0.7%) 2/289 (0.7%) 3/286 (1%)
    Hypomagnesemia 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Hyponatremia 53/1477 (3.6%) 5/284 (1.8%) 5/289 (1.7%) 12/286 (4.2%)
    Hypophosphatemia 8/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 15/1477 (1%) 1/284 (0.4%) 1/289 (0.3%) 1/286 (0.3%)
    Avascular necrosis 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Back pain 3/1477 (0.2%) 0/284 (0%) 3/289 (1%) 1/286 (0.3%)
    Bone pain 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Chest wall pain 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Flank pain 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Generalized muscle weakness 28/1477 (1.9%) 1/284 (0.4%) 2/289 (0.7%) 4/286 (1.4%)
    Muscle weakness lower limb 1/1477 (0.1%) 0/284 (0%) 2/289 (0.7%) 1/286 (0.3%)
    Muscle weakness upper limb 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Myalgia 17/1477 (1.2%) 1/284 (0.4%) 1/289 (0.3%) 1/286 (0.3%)
    Pain in extremity 4/1477 (0.3%) 0/284 (0%) 1/289 (0.3%) 2/286 (0.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms - Other 4/1477 (0.3%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Nervous system disorders
    Ataxia 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Cognitive disturbance 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Concentration impairment 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Dizziness 5/1477 (0.3%) 0/284 (0%) 1/289 (0.3%) 1/286 (0.3%)
    Encephalopathy 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Headache 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 2/286 (0.7%)
    Hydrocephalus 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Memory impairment 1/1477 (0.1%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Neuralgia 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Paresthesia 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Peripheral motor neuropathy 6/1477 (0.4%) 1/284 (0.4%) 0/289 (0%) 2/286 (0.7%)
    Peripheral sensory neuropathy 30/1477 (2%) 1/284 (0.4%) 4/289 (1.4%) 7/286 (2.4%)
    Reversible posterior leukoencephalopathy 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Syncope 10/1477 (0.7%) 2/284 (0.7%) 1/289 (0.3%) 1/286 (0.3%)
    Nervous system disorders - Other 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Psychiatric disorders
    Confusion 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Delirium 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Depression 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Hallucinations 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Insomnia 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Renal and urinary disorders
    Hematuria 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Proteinuria 8/1477 (0.5%) 12/284 (4.2%) 1/289 (0.3%) 8/286 (2.8%)
    Renal and urinary disorders - Other 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Reproductive system and breast disorders
    Irregular menstruation 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Bronchopleural fistula 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Bronchopulmonary hemorrhage 5/1477 (0.3%) 0/284 (0%) 0/289 (0%) 2/286 (0.7%)
    Cough 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Dyspnea 21/1477 (1.4%) 2/284 (0.7%) 5/289 (1.7%) 7/286 (2.4%)
    Epistaxis 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Hypoxia 3/1477 (0.2%) 0/284 (0%) 2/289 (0.7%) 4/286 (1.4%)
    Pleural effusion 1/1477 (0.1%) 1/284 (0.4%) 0/289 (0%) 1/286 (0.3%)
    Pleural hemorrhage 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Pneumonitis 3/1477 (0.2%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Pneumothorax 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Pulmonary edema 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Pulmonary hypertension 0/1477 (0%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Respiratory failure 8/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Sore throat 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Wheezing 0/1477 (0%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Respiratory thoracic mediastinal - Other 7/1477 (0.5%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Hyperhidrosis 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Rash acneiform 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Rash maculo-papular 7/1477 (0.5%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Skin and subcutaneous tissue - Other 1/1477 (0.1%) 0/284 (0%) 1/289 (0.3%) 0/286 (0%)
    Vascular disorders
    Hypertension 161/1477 (10.9%) 47/284 (16.5%) 13/289 (4.5%) 54/286 (18.9%)
    Hypotension 15/1477 (1%) 0/284 (0%) 1/289 (0.3%) 2/286 (0.7%)
    Peripheral ischemia 0/1477 (0%) 1/284 (0.4%) 0/289 (0%) 0/286 (0%)
    Thromboembolic event 46/1477 (3.1%) 5/284 (1.8%) 1/289 (0.3%) 4/286 (1.4%)
    Visceral arterial ischemia 1/1477 (0.1%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Vascular disorders - Other, specify 2/1477 (0.1%) 0/284 (0%) 0/289 (0%) 1/286 (0.3%)
    Other (Not Including Serious) Adverse Events
    Arm I (Induction Therapy - Carboplatin, Paclitaxel & Bevacizumab) Arm A (Maintenance Therapy - Bevacizumab) Arm B (Maintenance Therapy - Pemetrexed) Arm C (Maintenance Therapy - Bevacizumab + Pemetrexed)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1178/1477 (79.8%) 216/284 (76.1%) 222/289 (76.8%) 237/286 (82.9%)
    Blood and lymphatic system disorders
    Anemia 144/1477 (9.7%) 10/284 (3.5%) 33/289 (11.4%) 36/286 (12.6%)
    Gastrointestinal disorders
    Constipation 113/1477 (7.7%) 10/284 (3.5%) 15/289 (5.2%) 27/286 (9.4%)
    Diarrhea 101/1477 (6.8%) 2/284 (0.7%) 15/289 (5.2%) 14/286 (4.9%)
    Mucositis oral 0/1477 (0%) 3/284 (1.1%) 7/289 (2.4%) 17/286 (5.9%)
    Nausea 235/1477 (15.9%) 18/284 (6.3%) 37/289 (12.8%) 52/286 (18.2%)
    Vomiting 93/1477 (6.3%) 3/284 (1.1%) 14/289 (4.8%) 21/286 (7.3%)
    General disorders
    Fatigue 528/1477 (35.7%) 79/284 (27.8%) 118/289 (40.8%) 125/286 (43.7%)
    Investigations
    Creatinine increased 0/1477 (0%) 0/284 (0%) 8/289 (2.8%) 17/286 (5.9%)
    Lymphocyte count decreased 78/1477 (5.3%) 6/284 (2.1%) 33/289 (11.4%) 30/286 (10.5%)
    Platelet count decreased 93/1477 (6.3%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Weight loss 86/1477 (5.8%) 20/284 (7%) 17/289 (5.9%) 28/286 (9.8%)
    White blood cell decreased 86/1477 (5.8%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Metabolism and nutrition disorders
    Anorexia 294/1477 (19.9%) 33/284 (11.6%) 54/289 (18.7%) 62/286 (21.7%)
    Dehydration 83/1477 (5.6%) 0/284 (0%) 0/289 (0%) 0/286 (0%)
    Hypoalbuminemia 0/1477 (0%) 10/284 (3.5%) 9/289 (3.1%) 17/286 (5.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 201/1477 (13.6%) 11/284 (3.9%) 18/289 (6.2%) 16/286 (5.6%)
    Myalgia 162/1477 (11%) 13/284 (4.6%) 14/289 (4.8%) 16/286 (5.6%)
    Nervous system disorders
    Dysgeusia 103/1477 (7%) 10/284 (3.5%) 19/289 (6.6%) 19/286 (6.6%)
    Peripheral sensory neuropathy 206/1477 (13.9%) 41/284 (14.4%) 44/289 (15.2%) 50/286 (17.5%)
    Renal and urinary disorders
    Proteinuria 0/1477 (0%) 41/284 (14.4%) 2/289 (0.7%) 39/286 (13.6%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 98/1477 (6.6%) 14/284 (4.9%) 23/289 (8%) 36/286 (12.6%)
    Skin and subcutaneous tissue disorders
    Alopecia 758/1477 (51.3%) 113/284 (39.8%) 115/289 (39.8%) 115/286 (40.2%)
    Vascular disorders
    Hypertension 265/1477 (17.9%) 87/284 (30.6%) 49/289 (17%) 111/286 (38.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Study Statistician
    Organization ECOG-ACRIN Biostatistics Center
    Phone 617-632-3012
    Email eatrials@jimmy.harvard.edu
    Responsible Party:
    ECOG-ACRIN Cancer Research Group
    ClinicalTrials.gov Identifier:
    NCT01107626
    Other Study ID Numbers:
    • E5508
    First Posted:
    Apr 21, 2010
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jun 1, 2022