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tnAcity: Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01881230
Collaborator
(none)
191
Enrollment
140
Locations
3
Arms
37.1
Actual Duration (Months)
1.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of nab-paclitaxel in combination with either gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line treatment in female subjects with triple negative metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed Description

ABI-007-MBC- 001 is a Phase 2/3, multicenter, open-label, randomized, study that will compare the safety and efficacy of weekly nab-paclitaxel in combination with gemcitabine or carboplatin to the combination of gemcitabine and carboplatin as first line therapy in female subjects with Estrogen Receptor (ER), Progesterone Receptor (PgR), and human epidermal growth factor receptor 2 (HER2) negative (triple negative) metastatic breast cancer (TNMBC) or metastatic triple negative breast cancer. In the phase 2 portion of the study, the combinations of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus carboplatin will be evaluated, and a comparator arm of gemcitabine combined with carboplatin will be used. In the phase 3 portion of the study, the selected nab-paclitaxel combination treatment will be compared to gemcitabine combined with carboplatin to evaluate progression free survival, safety and tolerability, overall survival, disease control rate and duration of response in women with metastatic triple negative breast cancer.

Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.

Study Design

Study Type:
Interventional
Actual Enrollment :
191 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer
Actual Study Start Date :
Sep 26, 2013
Actual Primary Completion Date :
Oct 28, 2016
Actual Study Completion Date :
Oct 28, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: nab-Paclitaxel plus Gemcitabine

Treatment Arm A: nab-Paclitaxel 125 mg/m^2 by intravenous (IV) administration over 30 minutes, followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day cycle by IV administration over 30 minutes

Drug: nab-Paclitaxel
nab-Paclitaxel 125 mg/m^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.
Other Names:
  • Abraxane

    • Drug: Gemcitabine
    Gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day treatment cycle.
    Other Names:
  • Gemzar

    		•
    Experimental: nab-Paclitaxel plus Carboplatin

    Treatment Arm B: nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin at an Area Under the Curve (AUC) of 2 on Days 1 and 8 of each 21-day cycle by IV administration

    Drug: nab-Paclitaxel
    nab-Paclitaxel 125 mg/m^2 by IV administration over 30 minutes on Days 1 and 8 of each 21-day treatment cycle.
    Other Names:
  • Abraxane

    • Drug: Carboplatin
    Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration
    Other Names:
  • Paraplatin,
  • Paraplatin AQ

    		•
    Active Comparator: Gemcitabine plus Carboplatin

    Treatment Arm C: Gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin AUC 2 on Days 1 and 8 of each 21-day cycle by IV administration

    Drug: Carboplatin
    Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration
    Other Names:
  • Paraplatin,
  • Paraplatin AQ

    • Drug: Gemcitabine
    Gemcitabine 1000 mg/m^2 on Days 1 and 8 of each 21-day treatment cycle.
    Other Names:
  • Gemzar

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment. [From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C]

      PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.

    Secondary Outcome Measures

    1. Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment. [Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C]

      Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

    2. Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy [Cycle 6]

      The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.

    3. Kaplan-Meier Estimates of Overall Survival [From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C]

      Overall survival was defined as the time from the date of randomization to the date of death (from any cause).

    4. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C]

      Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.

    5. Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions) [From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C]

      The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

    6. Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs [From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C]

      Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria are met:

    1. Female subjects, age ≥ 18 years at the time informed consent is signed

    2. Pathologically confirmed adenocarcinoma of the breast

    3. Pathologically confirmed as triple negative, source documented, defined as both of the following

    4. Estrogen Receptor (ER) and Progesterone Receptor (PgR) negative: < 1% of tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER or PgR (positive intrinsic controls)

    5. Human Epidermal Growth Factor Receptor 2 (HER2) negative as per American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines i. Immunohistochemistry (IHC) 0 or 1 Fluorescence In Situ Hybridization (FISH) negative (or equivalent negative test). Subjects with IHC 2 must have a negative by Fluorescence In Situ Hybridization (FISH),, (or equivalent negative test).

    6. Subjects with prior breast cancer history of different phenotypes (ie, ER/PgR/HER2 positive) must have pathologic confirmation of triple negative disease in at least one of the current sites of metastasis

    7. Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy; unless (a) anthracycline treatment was not indicated or was not the best treatment option for the subject in the opinion of the treating physician; and (b) anthracycline treatment remains not indicated or, in the opinion of the treating physician, is not the best treatment option for the subject's metastatic disease.

    1. Newly diagnosed subjects presenting with TNMBC are eligible for the study if anthracycline treatment is not indicated or is not the best treatment option for the subject in the opinion of the treating physician.

    1. Subjects with measurable metastatic disease, defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines

    2. Life expectancy ≥ 16 weeks from randomization

    3. No prior cytotoxic chemotherapy for metastatic breast cancer. Prior immunotherapy and/or monoclonal antibody therapy are acceptable. Prior treatments must have been discontinued at least 30 days prior to start of study treatment and all related toxicities must have resolved to Grade 1 or less.

    4. Prior neoadjuvant or adjuvant chemotherapy, if given, must have been completed at least 6 months before randomization with all related toxicities resolved, and documented evidence of disease progression per RECIST 1.1 guidelines is required.

    1. If prior neoadjuvant or adjuvant chemotherapy contained taxane, gemcitabine, or platinum agents, the treatment must have completed at least 12 months before randomization

    1. Prior radiotherapy must have completed before randomization, with full recovery from acute radiation side effects. At least one measurable lesion must be completely outside the radiation portal or there must be unequivocal radiologic or clinical exam proof of progressive disease within the radiation portal, in accordance with RECIST 1.1 guidelines

    2. At least 30 days from major surgery before randomization, with full recovery

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

    4. Subject has the following blood counts at screening:

    • Absolute Neutrophil Count (ANC) ≥ 1500/mm^2 ;

    • Platelets ≥ 100,000/mm^2 ;

    • Hemoglobin (Hgb) ≥ 9 g/dL

    1. Subject has the following blood chemistry levels at screening:

    • Aspartate aminotransferase (AST) Serum glutamic-oxaloacetic transaminase (SGOT), Alanine Aminotransferase (ALT ) Serum Glutamic Pyruvate Transaminase (SGPT) ≤ 2.5 x upper limit of normal range (ULN); if hepatic metastases present ≤ 5.0 x ULN

    • Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in subjects with documented Gilbert's Syndrome

    • Creatinine clearance > 60 mL/min (by Cockcroft-Gault)

    1. Females of child-bearing potential [defined as a sexually mature women who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months)] must:

    • Demonstrate a negative serum pregnancy test result at screening (performed by central lab) confirmed by local negative urine pregnancy dipstick within 72 hours prior to the first dose of IP); pregnancy test with sensitivity of at least 25 mIU/mL; and

    • Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, two physician approved effective contraception methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) without interruption for 28 days or longer as required by local guidelines, prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of the study or longer as required by local guidelines

    1. Females must abstain from breastfeeding starting at randomization, during study participation and for 28 days or longer as required by local guidelines, after IP discontinuation

    2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted

    3. Able to adhere to the study visit schedule and other protocol requirements

    Exclusion Criteria:

    A subject will not be eligible for inclusion in this study if any of the following criteria apply:

    1. Male subjects

    2. Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior immunotherapy & monoclonal antibody therapy are acceptable.

    3. Subjects who received prior cytotoxic chemotherapy after incomplete resection of locoregional recurrent disease

    4. History of, or known current evidence of brain metastasis, including leptomeningeal involvement.

    5. Subjects with bone as the only site of metastatic disease

    6. Subjects with regional lymph node as the only site of metastatic disease

    7. Serious intercurrent medical or psychiatric illness, including serious active infection

    8. History of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization

    9. History of other primary malignancy in the last 5 years prior to randomization. Subjects with prior breast cancer history are eligible, however, the most recently obtained biopsy must demonstrate triple negative disease (source documented). Subjects with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.

    10. Subjects with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple uncontrolled or unstable allergies which, in the opinion of the investigator, may lead to serious complications

    11. Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

    12. Subjects who have received an investigational product within the previous 4 weeks prior to randomization

    13. Subject is currently enrolled, or will enroll in a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study

    14. Pregnant or nursing women

    15. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or any other platin, or nucleoside analogue agents

    16. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

    17. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if she were to participate in the study

    18. Any condition that confounds the ability to interpret data from the study

    19. History of seropositive human immunodeficiency virus (HIV)

    20. Subjects who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer and Research Center Chandler Arizona United States 85224
    2 Arizona Center for Cancer Care Glendale Arizona United States 85306
    3 Arizona Cancer Research Alliance Scottsdale Arizona United States 85251
    4 Mayo Clinic Arizona Scottsdale Arizona United States 85259
    5 Highlands Oncology Group Fayetteville Arkansas United States 72703
    6 Pacific Cancer Medical Center Inc Anaheim California United States 92801
    7 California Cancer Associates for Research and Excellence cCARE Escondido California United States 92025
    8 University of California San Diego Moores Cancer Center La Jolla California United States 92093
    9 Wilshire Oncology Medical Group, Inc La Verne California United States 91750
    10 Translational Research Management Los Angeles California United States 90045
    11 Coastal Integrative Cancer Care San Luis Obispo California United States 93401
    12 Central Coast Medical Oncology Corporation Santa Maria California United States 93454
    13 Redwood Regional Medical Group, INC Santa Rosa California United States 95403
    14 Center for Hematology-Oncology Boca Raton Florida United States 33486
    15 Memorial Breast Cancer Center Hollywood Florida United States 33021
    16 Mayo Clinic - Jacksonville Jacksonville Florida United States 32224
    17 University of Miami School of Medicine Miami Florida United States 33136
    18 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    19 Florida Cancer Specialists Sarasota Florida United States 34232
    20 Florida Cancer Specialists West Palm Beach Florida United States 33401
    21 Joliet Oncology-Hematology Associates, Ltd Joliet Illinois United States 60435
    22 Carle Cancer Center Urbana Illinois United States 61801
    23 Investigative Clinical Research of Indiana, LLC Indianapolis Indiana United States 46254
    24 University of South Alabama Mitchell Cancer Institute Lafayette Louisiana United States 70503
    25 University of Maryland School of Med Baltimore Maryland United States 21201
    26 Center for Cancer and Blood Disorders, PC Bethesda Maryland United States 20817
    27 Henry Ford Medical Center - New Center One Detroit Michigan United States 48202-268
    28 Minnesota Oncology Hematology, PA Minneapolis Minnesota United States 55407
    29 Mayo Clinic Rochester Minnesota United States 55905
    30 Midwest Physicians Group Kansas City Missouri United States 64132
    31 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
    32 New Hampshire Oncology Hematology Hooksett New Hampshire United States 03106
    33 Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon New Hampshire United States 03756
    34 Englewood Hospital and Medical Center Englewood New Jersey United States 07631
    35 Hematology Oncology Associates of CNY East Syracuse New York United States 13057
    36 NYU Langone Arena Oncology Lake Success New York United States 11042
    37 Clinical Research Alliance New York New York United States 10021
    38 Alamance Regional Medical Cancer Center Burlington North Carolina United States 27215-8700
    39 University of Cincinnatti Cincinnati Ohio United States 45219
    40 Oncology Hematology Care Cincinnati Ohio United States 45242
    41 Mark H Zangmeister Center Columbus Ohio United States 43219
    42 Toledo Community Oncology Program Toledo Ohio United States 43623
    43 Cancer Centers of Southwest Oklahoma Lawton Oklahoma United States 73505
    44 North Bend Medical Center Coos Bay Oregon United States 97420
    45 Northwest Cancer Specialists, P.C. - Hoyt Portland Oregon United States 97213
    46 Providence Portland Medical Center Portland Oregon United States 97213
    47 St Mary Medical Center Langhorne Pennsylvania United States 19047
    48 Magee Women's Hospital Pittsburgh Pennsylvania United States 15213
    49 South Carolina Oncology Associates Columbia South Carolina United States 29210
    50 Chattanooga Oncology Hematology Associates Chattanooga Tennessee United States 37404
    51 Sarah Cannon Cancer Center Nashville Tennessee United States 37203
    52 Texas Oncology, PA Dallas Texas United States 75231
    53 Texas Oncology, PA- Dallas Dallas Texas United States 75246
    54 The Center for Cancer and Blood Disorders Fort Worth Texas United States 76104
    55 UT Physicians General Medicine Houston Texas United States 77030
    56 Cancer Care Centers of South Texas - Loop San Antonio Texas United States 78217
    57 Texas Oncology P.A.- Tyler Tyler Texas United States 75702
    58 Hematology Oncology Associates of Fredericksburg Fredericksburg Virginia United States 22408
    59 Delta Hematologyoncology Associates Portsmouth Virginia United States 23704
    60 Virginia Cancer Institute Richmond Virginia United States 23230
    61 Medical Oncology Associates Spokane Washington United States 99208
    62 Edwards Comprehensive Cancer Center Huntington West Virginia United States 25701
    63 Saint Vincent Hospital Green Bay Wisconsin United States 54301
    64 Columbia St Marys Cancer Center Milwaukee Wisconsin United States 53211
    65 Canberra Hospital Garran Australian Capital Territory Australia 2605
    66 Frankston Hospital Oncology Research Frankston Victoria Australia 3199
    67 Border Medical Oncology Wodonga Victoria Australia 3690
    68 Sir Charles Gairdner Hospital Nedlands Australia 6009
    69 Universitaetsklinik Innsbruck Innsbruck Austria 6020
    70 Salzburger Landkliniken St. Johanns-Spital Salzburg Austria 5020
    71 Medizinische Universitat Wien Vienna Austria 1090
    72 Centro de Oncologia Da Bahia Salvador Bahia Brazil 41820-021
    73 Liga Paranaense de Combate Ao Cancer Curitiba Paraná Brazil 81520-060
    74 Instituto Nacional de Cancer - INCA Rio De Janerio Rio De Janeiro Brazil 20560-120
    75 Associacao Hospitalar Moinhos de Vento Hospital Moinhos de Vento Porto Alegre Rio Grande Do Sul Brazil 90035-001
    76 Hospital Sao Lucas - PUCRS Porto Alegre Rio Grande Do Sul Brazil 90610-000
    77 Fundacao Pio XII - Hospital de Cancer de Barretos Barretos São Paulo Brazil 14784-400
    78 Hospital Dr. Amaral Carvalho/ Hospital Amaral Carvalho Jaú Jau/SP São Paulo Brazil 17210-080
    79 ONCOCLINIC Clinica de Oncologia LTDA Fortaleza Brazil 60160-230
    80 Instituto Ribeiraopretano de Combate Ao Cancer Ribeirao Preto Brazil 14015-130
    81 Hospital das Clinicas da Faculdade de Medicina da USP Ribeirao Preto Brazil 14048-900
    82 Hospital Bruno Born Rio Grande Do Sul Brazil 95900-000
    83 Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto Brazil 15090-000
    84 Hospital Albert Einstein Sociedade Beneficente Israelita Brasileira Sao Paulo Brazil 05651-901
    85 Sociedade Beneficente de Senhoras Hospital Sirio Libanes São Paulo Brazil 01308-050
    86 Instituto Brasileiro de Controle Do Cancer IBCC São Paulo Brazil 03102-002
    87 Ottawa General Hospital Ottawa Ontario Canada K1H 8L6
    88 CHUM - Notre Dame Montreal Quebec Canada H2L 4M1
    89 Hospital du Saint Scarement Sacrement Laboratory Quebec City Quebec Canada G1S4L8
    90 CSSS de Rimouski Neigette Rimouski Quebec Canada G5L5T1
    91 Alan Blair Cancer Centre at Pasqua Hosptial Regina Saskatchewan Canada S4T1A5
    92 Centre Jean Perrin Clermont-Ferrand France 63003
    93 Sankt Gertrauden-Krankenhaus Berlin Germany 10713
    94 Facharztpraxis fur Gynakologie und Geburtshilfe Bonn Germany 53111
    95 Agaplesion Markus Krankenhaus Frankfurt Germany 60431
    96 Praxis fur interdisziplinare Onkologie & Hamatologie Freiburg Germany 79110
    97 Universitaetsklinikum Heidelberg Heidelberg Germany 69120
    98 Frauenarzte am Bahnhofsplatz Hildesheim Germany 31134
    99 Schwerpunktpraxis fur Gynakologische Onkologie Köln Germany 50679
    100 LMU Klinikum der Universitat München Germany 81377
    101 Krankenanstalt Mutterhaus der Borromaerinnen Trier Germany 54290
    102 Universitatsklinikum Ulm Ulm Germany 89075
    103 University of Athens Medical school - Regional General Hospital Athens Greece 11528
    104 IASO General Athens Greece 15562
    105 Metropolitan Hospital Faliro Greece 18547
    106 University General Hospital of Heraklion Heraklion Greece 71110
    107 University General Hospital of Patras Rio Patras Greece 26500
    108 Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna, Emilia-Romagna Italy 40138
    109 Azienda Ospedaliero-Universitaria di Ferrara Arcispedale Sant' Anna Ferrara Italy 44124
    110 IRCCS AziendaOspedaliera Universitaria San Martino Genova Italy 16132
    111 Presidio Ospedaliero della Misericordia Grosseto Italy 58100
    112 Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte Messina Italy 98158
    113 Azienda Ospedaliera San Gerardo Monza Italy 20900
    114 Azienda Ospedaliera Universitaria Federico II Napoli, Campania Italy 80131
    115 Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Napoli, Campania Italy 80131
    116 Istituto Oncologico Veneto Padova Italy 35128
    117 Arcispedale Santa Maria Nuova Reggio Emilia Italy 42100
    118 Policlinico Universitario A Gemelli Roma Italy 00168
    119 Azienda Ospedaliera Sant Andrea Roma Italy 00189
    120 Istituto Nazionale Tumori Regina Elena Roma Italy 144
    121 Istituto Clinico Humanitas Rozzano (MI) Italy 20089
    122 Azienda Ospedaliera Citta della Salute e della Scienza di Torino Torino, Piemonte Italy 10126
    123 Azienda Ospedaliera Treviglio-Caravaggio Treviglio Italy 24047
    124 Hospital Espirito Santo Evora Portugal 7000-811
    125 Hospital Da Luz Lisboa Portugal 1500-650
    126 Hospital de Santa Maria Lisboa Portugal 1649-035
    127 Instituto Portugues de Oncologia do Porto, Francisco Gentil Porto Portugal 4200-072
    128 Clinic Barcelona Hospital Universitari Barcelona Spain 08036
    129 Hospital Universitario Vall D Hebron Barcelona Spain 8035
    130 Hospital Universitario Reina Sofia Cordoba Spain 14004
    131 Hospital General Gregorio Maranon Madrid Spain 28007
    132 Onkologikoa - Kutxaren Institutu Onkologikoa San Sebastian Spain 20014
    133 Hospital Clinico Universitario de Santiago Santiago de Compostela Spain 15706
    134 Hospital Universitario Virgen Macarena Sevilla Spain 41071
    135 Hospital Universitario Miguel Servet Zaragoza Spain 50009
    136 Royal United Hospital Bath United Kingdom BA1 3NG
    137 Sarah Cannon Research Institute UK London United Kingdom W1G 6AD
    138 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
    139 The East and North Hertfordshire NHS Trust Middlesex United Kingdom HA62RN
    140 Sheffield Teaching Hospitals NHS Foundation Trust Sheffield South Yorkshire United Kingdom S10 2SJ

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Ileana Elias, M.D., Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01881230
    Other Study ID Numbers:
    • ABI-007-MBC-001
    • 2013-000113-20
    First Posted:
    Jun 19, 2013
    Last Update Posted:
    Feb 21, 2019
    Last Verified:
    Feb 1, 2019
    Keywords provided by Celgene
    Breast Cancer
    Cancer of the Breast
    Metastatic Breast Cancer
    Metastatic Triple Negative Breast Cancer
    Triple Negative Breast Cancer
    Triple Negative Metastatic Breast Cancer
    Basal-like breast cancer
    Hormone receptor negative breast cancer
    Estrogen receptor negative breast cancer
    Progesterone negative receptor breast cancer
    HER2 Negative Breast Cancer
    Abraxane
    nab-Paclitaxel
    ABI-007
    gemcitabine
    Gemzar
    carboplatin
    Paraplatin
    Paraplatin AQ
    Phase 2
    Phase 3
    Additional relevant MeSH terms:
    Breast Neoplasms
    Triple Negative Breast Neoplasms
    Gemcitabine
    Paclitaxel
    Carboplatin

    Study Results

    Participant Flow

    Recruitment Details This multicenter study was conducted by investigators in 11 countries in North America, Europe, Australia and South America, and enrolled participants at a total of 86 sites. Due to changes in the treatment landscape since the initiation of this trial, the decision was made not to proceed to the Phase 3 portion of the study.
    Pre-assignment Detail Participants were randomized 1:1:1, stratified by disease free interval (≤ 1 year; > 1 year).
    Arm/Group Title Arm A: Nab-Paclitaxel Plus (+) Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Period Title: Overall Study
    STARTED 61 64 66
    Safety Population 60 64 64
    Treatment Discontinued 60 64 64
    COMPLETED 0 0 0
    NOT COMPLETED 61 64 66

    Baseline Characteristics

    Arm/Group Title Arm A: Nab-Paclitaxel Plus (+) Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin Total
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Total of all reporting groups
    Overall Participants 61 64 66 191
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.7
    (12.16)
    54.3
    (11.96)
    56.7
    (10.87)
    54.9
    (11.67)
    Sex: Female, Male (Count of Participants)
    Female
    61
    100%
    64
    100%
    66
    100%
    191
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (Count of Participants)
    Black or African American
    9
    14.8%
    6
    9.4%
    8
    12.1%
    23
    12%
    White
    50
    82%
    55
    85.9%
    54
    81.8%
    159
    83.2%
    Unknown or Not Reported
    2
    3.3%
    3
    4.7%
    4
    6.1%
    9
    4.7%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    0 = Fully Active
    34
    55.7%
    38
    59.4%
    42
    63.6%
    114
    59.7%
    1 = Restrictive but ambulatory
    25
    41%
    26
    40.6%
    22
    33.3%
    73
    38.2%
    2 = Ambulatory but unable to work
    1
    1.6%
    0
    0%
    0
    0%
    1
    0.5%
    Missing
    1
    1.6%
    0
    0%
    2
    3%
    3
    1.6%
    Disease Free Interval by Clinical Interpretation (Years) [Number]
    ≤ 1 year
    17
    16
    20
    53
    > 1 year
    43
    48
    45
    136
    Missing
    1
    0
    1
    2
    Time from Diagnosis to First Documented Disease/Relapse (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    38.8
    (49.46)
    29.9
    (37.18)
    50.9
    (62.60)
    40.0
    (51.46)
    Time from First Documented Metastatic Disease/Relapse to Study Randomization (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    2.1
    (5.08)
    4.2
    (18.39)
    1.6
    (1.70)
    2.6
    (11.07)
    Time from Primary Diagnosis to Randomization (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    43.7
    (54.60)
    35.5
    (40.51)
    52.5
    (62.37)
    44.0
    (53.53)
    Current Sites of Metastasis (participants) [Number]
    Lymph Nodes(s)
    38
    62.3%
    50
    78.1%
    51
    77.3%
    139
    72.8%
    Lung/Thoracic
    42
    68.9%
    42
    65.6%
    41
    62.1%
    125
    65.4%
    Bone
    23
    37.7%
    21
    32.8%
    25
    37.9%
    69
    36.1%
    Liver
    17
    27.9%
    16
    25%
    23
    34.8%
    56
    29.3%
    Right/Left Breast
    15
    24.6%
    19
    29.7%
    17
    25.8%
    51
    26.7%
    Skin/Soft Tissue
    13
    21.3%
    13
    20.3%
    8
    12.1%
    34
    17.8%
    Other
    13
    21.3%
    10
    15.6%
    8
    12.1%
    31
    16.2%
    Abdomen/Peritoneal
    1
    1.6%
    2
    3.1%
    3
    4.5%
    6
    3.1%
    Stage of Primary Diagnosis (Count of Participants)
    Stage 0
    0
    0%
    1
    1.6%
    0
    0%
    1
    0.5%
    Stage IA
    7
    11.5%
    6
    9.4%
    11
    16.7%
    24
    12.6%
    Stage IB
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Stage IIA
    14
    23%
    9
    14.1%
    15
    22.7%
    38
    19.9%
    Stage IIB
    8
    13.1%
    7
    10.9%
    9
    13.6%
    24
    12.6%
    Stage IIIA
    9
    14.8%
    10
    15.6%
    3
    4.5%
    22
    11.5%
    Stage IIIB
    3
    4.9%
    3
    4.7%
    5
    7.6%
    11
    5.8%
    Stage IIIC
    3
    4.9%
    3
    4.7%
    2
    3%
    8
    4.2%
    Stage IV
    11
    18%
    17
    26.6%
    10
    15.2%
    38
    19.9%
    Triple-Negative Breast Cancer (TNBC) at Primary Diagnosis (Count of Participants)
    Count of Participants [Participants]
    51
    83.6%
    53
    82.8%
    48
    72.7%
    152
    79.6%
    Triple-Negative at Latest Diagnosis (Count of Participants)
    Count of Participants [Participants]
    60
    98.4%
    62
    96.9%
    65
    98.5%
    187
    97.9%

    Outcome Measures

    1. Primary Outcome
    Title Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.
    Description PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir.
    Time Frame From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

    Outcome Measure Data

    Analysis Population Description
    ITT includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment prior to the data cutoff date.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 61 64 66
    Median (95% Confidence Interval) [months]
    5.5
    8.3
    6.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Nab-Paclitaxel + Gemcitabine, Arm B: Nab-Paclitaxel + Carboplatin
    Comments For stratified analysis, the stratified log-rank test and stratified Cox proportional hazards model were used, where the stratification factor is the disease free interval (<= 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0183
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.692
    Confidence Interval (2-Sided) 95%
    1.089 to 2.629
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm B: Nab-Paclitaxel + Carboplatin, Arm C: Gemcitabine + Carboplatin
    Comments For stratified analysis, the stratified log-rank test and stratified Cox proportional hazards model were used, where the stratification factor is the disease free interval (<= 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0152
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.581
    Confidence Interval (2-Sided) 95%
    0.373 to 0.904
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A: Nab-Paclitaxel + Gemcitabine, Arm C: Gemcitabine + Carboplatin
    Comments For stratified analysis, the stratified log-rank test and stratified Cox proportional hazards model were used, where the stratification factor is the disease free interval (<= 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.8599
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.039
    Confidence Interval (2-Sided) 95%
    0.676 to 1.597
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.
    Description Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.
    Time Frame Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

    Outcome Measure Data

    Analysis Population Description
    ITT includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment prior to the data cutoff date.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 61 64 66
    Number (95% Confidence Interval) [percentage of participants]
    39.3
    64.4%
    73.4
    114.7%
    43.9
    66.5%
    3. Secondary Outcome
    Title Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy
    Description The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications.
    Time Frame Cycle 6

    Outcome Measure Data

    Analysis Population Description
    ITT includes all randomized participants regardless of whether they received any IP or had any efficacy assessments collected. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment prior to the data cutoff date.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 61 64 66
    Number (95% Confidence Interval) [percentage of participants]
    55.7
    91.3%
    64.1
    100.2%
    50.0
    75.8%
    4. Secondary Outcome
    Title Kaplan-Meier Estimates of Overall Survival
    Description Overall survival was defined as the time from the date of randomization to the date of death (from any cause).
    Time Frame From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

    Outcome Measure Data

    Analysis Population Description
    The ITT population includes all randomized participants regardless of whether the participant received any Investigational Product (IP) or had any efficacy assessments collected.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 61 64 66
    Median (95% Confidence Interval) [months]
    12.1
    16.8
    12.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A: Nab-Paclitaxel + Gemcitabine, Arm B: Nab-Paclitaxel + Carboplatin
    Comments Hazard ratios and associated two-sided 95% confidence intervals were estimated using stratified Cox proportional hazard model. The stratification factor is the disease free interval (≤ 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1579
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.375
    Confidence Interval (2-Sided) 95%
    0.882 to 2.143
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm B: Nab-Paclitaxel + Carboplatin, Arm C: Gemcitabine + Carboplatin
    Comments Hazard ratios and associated two-sided 95% confidence intervals were estimated using stratified Cox proportional hazard model. The stratification factor is the disease free interval (≤ 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2945
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.796
    Confidence Interval (2-Sided) 95%
    0.520 to 1.221
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm A: Nab-Paclitaxel + Gemcitabine, Arm C: Gemcitabine + Carboplatin
    Comments Hazard ratios and associated two-sided 95% confidence intervals were estimated using stratified Cox proportional hazard model. The stratification factor is the disease free interval (≤ 1 year; > 1 year).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.6691
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.101
    Confidence Interval (2-Sided) 95%
    0.710 to 1.708
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
    Description Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death.
    Time Frame From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all randomized participants who received at least 1 dose of IP.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 60 64 64
    Any TEAE
    60
    98.4%
    63
    98.4%
    64
    97%
    Any Grade 3 or Higher TEAE
    46
    75.4%
    51
    79.7%
    54
    81.8%
    Treatment-related TEAE
    59
    96.7%
    62
    96.9%
    60
    90.9%
    Treatment-related, Grade 3 or Higher TEAE
    35
    57.4%
    43
    67.2%
    46
    69.7%
    Serious TEAE
    22
    36.1%
    20
    31.3%
    25
    37.9%
    Treatment-related Serious TEAE
    10
    16.4%
    9
    14.1%
    13
    19.7%
    TEAE Leading to Discontinuation (D/C) of IP
    16
    26.2%
    29
    45.3%
    15
    22.7%
    Treatment Related (TR) TEAE Leading to D/C of IP
    12
    19.7%
    27
    42.2%
    12
    18.2%
    TEAE Leading to Dose Reduction (DR) of IP
    23
    37.7%
    20
    31.3%
    25
    37.9%
    Treatment related TEAE Leading to DR of IP
    23
    37.7%
    20
    31.3%
    23
    34.8%
    TEAE Leading to Dose Interruption (DI) of IP
    31
    50.8%
    50
    78.1%
    50
    75.8%
    TR TEAE Leading to DI of IP
    27
    44.3%
    44
    68.8%
    44
    66.7%
    TEAE leading to D/C of nab-Paclitaxel
    16
    26.2%
    17
    26.6%
    0
    0%
    TR TEAE leading to D/C of nab-Paclitaxel
    11
    18%
    13
    20.3%
    0
    0%
    TEAE leading to DR of nab-Paclitaxel
    22
    36.1%
    19
    29.7%
    0
    0%
    TR TEAE leading to DR of nab-Paclitaxel
    21
    34.4%
    19
    29.7%
    0
    0%
    TEAE leading to DI of nab-Paclitaxel
    31
    50.8%
    50
    78.1%
    0
    0%
    TR TEAE leading to DI of nab-Paclitaxel
    27
    44.3%
    44
    68.8%
    0
    0%
    TEAE leading to D/C of Gemcitabine
    13
    21.3%
    0
    0%
    13
    19.7%
    TR TEAE leading to D/C of Gemcitabine
    7
    11.5%
    0
    0%
    9
    13.6%
    TEAE leading to DR of Gemcitabine
    18
    29.5%
    0
    0%
    25
    37.9%
    TR TEAE leading to DR of Gemcitabine
    18
    29.5%
    0
    0%
    23
    34.8%
    TEAE leading to DI of Gemcitabine
    31
    50.8%
    0
    0%
    49
    74.2%
    TR TEAE leading to DI of Gemcitabine
    24
    39.3%
    0
    0%
    43
    65.2%
    TEAE leading to D/C of Carboplatin
    0
    0%
    28
    43.8%
    15
    22.7%
    TR TEAE leading to D/C of Carboplatin
    0
    0%
    25
    39.1%
    12
    18.2%
    TEAE leading to DR of Carboplatin
    0
    0%
    17
    26.6%
    21
    31.8%
    TR TEAE leading to DR of Carboplatin
    0
    0%
    17
    26.6%
    20
    30.3%
    TEAE leading to DI of Carboplatin
    0
    0%
    50
    78.1%
    50
    75.8%
    TR TEAE leading to DI of Carboplatin
    0
    0%
    44
    68.8%
    43
    65.2%
    TEAE Leading to Death
    2
    3.3%
    1
    1.6%
    2
    3%
    Treatment Related TEAE leading to death
    1
    1.6%
    0
    0%
    1
    1.5%
    6. Secondary Outcome
    Title Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)
    Description The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
    Time Frame From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

    Outcome Measure Data

    Analysis Population Description
    The Safety/Treated population includes all randomized participants who received at least 1 dose of IP.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 60 64 64
    ≥ one DR for both IPs
    33.3
    54.6%
    46.9
    73.3%
    51.6
    78.2%
    ≥ one DI for both IPs
    38.3
    62.8%
    70.3
    109.8%
    73.4
    111.2%
    ≥ one dose missed for both IPs
    48.3
    79.2%
    45.3
    70.8%
    56.3
    85.3%
    7. Secondary Outcome
    Title Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs
    Description Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose.
    Time Frame From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

    Outcome Measure Data

    Analysis Population Description
    The Safety/Treated population includes all randomized participants who received at least 1 dose of IP.
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration of each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin area under the curve 2 (AUC 2) on Days 1 and 8 in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment. Participants received gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants continued treatment until progressive disease (PD), unacceptable toxicity, required palliative radiotherapy or surgical intervention of lesion(s), withdrawal from study treatment, withdrawal of study consent, participant refusal or the investigator felt it was no longer in the best interest of the participant to continue on treatment.
    Measure Participants 60 64 64
    Number (95% Confidence Interval) [percentage of participants]
    21.7
    35.6%
    26.6
    41.6%
    21.9
    33.2%

    Adverse Events

    Time Frame From randomization through to 28 days after the last dose of IP; up to the data cut-off date of 16 December 2016; AEs collected and monitored for 39 months.
    Adverse Event Reporting Description Maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B and 110.1 weeks for Arm C
    Arm/Group Title Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Arm/Group Description Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by intravenous (IV) administration followed by gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration in each 21-day treatment cycle. Participants received nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration followed by Carboplatin AUC 2 on Days 1 and 8 in each 21-day treatment cycle. Participants received Gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration in each 21-day treatment cycle.
    All Cause Mortality
    Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 22/60 (36.7%) 20/64 (31.3%) 25/64 (39.1%)
    Blood and lymphatic system disorders
    Anaemia 2/60 (3.3%) 2/64 (3.1%) 4/64 (6.3%)
    Febrile neutropenia 1/60 (1.7%) 3/64 (4.7%) 0/64 (0%)
    Neutropenia 1/60 (1.7%) 2/64 (3.1%) 2/64 (3.1%)
    Pancytopenia 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Thrombocytopenia 0/60 (0%) 0/64 (0%) 2/64 (3.1%)
    Cardiac disorders
    Acute myocardial infarction 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Atrial fibrillation 1/60 (1.7%) 0/64 (0%) 1/64 (1.6%)
    Cardiac failure 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Myocardial infarction 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Palpitations 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Pericardial effusion 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Gastrointestinal disorders
    Ascites 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Constipation 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Diverticular perforation 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Haematemesis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Haematochezia 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Haemorrhoidal haemorrhage 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Nausea 2/60 (3.3%) 0/64 (0%) 0/64 (0%)
    Small intestinal obstruction 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Vomiting 1/60 (1.7%) 1/64 (1.6%) 1/64 (1.6%)
    General disorders
    Fatigue 1/60 (1.7%) 0/64 (0%) 1/64 (1.6%)
    General physical health deterioration 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Multiple organ dysfunction syndrome 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Non-cardiac chest pain 0/60 (0%) 0/64 (0%) 2/64 (3.1%)
    Pain 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Pyrexia 4/60 (6.7%) 0/64 (0%) 0/64 (0%)
    Hepatobiliary disorders
    Hepatic failure 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Nodular regenerative hyperplasia 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Immune system disorders
    Drug hypersensitivity 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Infections and infestations
    Breast cellulitis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Bronchitis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Cellulitis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Clostridium difficile colitis 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Device related infection 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Device related sepsis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Endocarditis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Gastroenteritis viral 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Localised infection 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Lower respiratory tract infection 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Peritonitis 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Pneumonia 4/60 (6.7%) 1/64 (1.6%) 1/64 (1.6%)
    Respiratory tract infection 0/60 (0%) 0/64 (0%) 2/64 (3.1%)
    Sepsis 1/60 (1.7%) 0/64 (0%) 2/64 (3.1%)
    Upper respiratory tract infection 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Urinary tract infection 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Viral infection 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Injury, poisoning and procedural complications
    Femur fracture 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Dehydration 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Hypokalaemia 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Bone pain 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Muscular weakness 0/60 (0%) 0/64 (0%) 2/64 (3.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to bone 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Metastases to central nervous system 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Metastases to meninges 1/60 (1.7%) 1/64 (1.6%) 0/64 (0%)
    Nervous system disorders
    Cerebrovascular accident 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Depressed level of consciousness 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Headache 1/60 (1.7%) 1/64 (1.6%) 0/64 (0%)
    Seizure 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Sensory disturbance 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Transient ischaemic attack 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Psychiatric disorders
    Confusional state 1/60 (1.7%) 0/64 (0%) 1/64 (1.6%)
    Mental status changes 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Aspiration 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Atelectasis 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Cough 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Dyspnoea 2/60 (3.3%) 1/64 (1.6%) 2/64 (3.1%)
    Hypoxia 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Pleural effusion 1/60 (1.7%) 0/64 (0%) 2/64 (3.1%)
    Pneumonitis 0/60 (0%) 1/64 (1.6%) 0/64 (0%)
    Pneumothorax 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Pulmonary embolism 1/60 (1.7%) 2/64 (3.1%) 0/64 (0%)
    Respiratory distress 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Respiratory failure 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Respiratory tract congestion 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Skin and subcutaneous tissue disorders
    Rash 1/60 (1.7%) 0/64 (0%) 0/64 (0%)
    Vascular disorders
    Deep vein thrombosis 0/60 (0%) 1/64 (1.6%) 1/64 (1.6%)
    Thrombosis 0/60 (0%) 0/64 (0%) 1/64 (1.6%)
    Other (Not Including Serious) Adverse Events
    Arm A: Nab-Paclitaxel + Gemcitabine Arm B: Nab-Paclitaxel + Carboplatin Arm C: Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 59/60 (98.3%) 63/64 (98.4%) 62/64 (96.9%)
    Blood and lymphatic system disorders
    Anaemia 25/60 (41.7%) 33/64 (51.6%) 30/64 (46.9%)
    Leukopenia 4/60 (6.7%) 12/64 (18.8%) 14/64 (21.9%)
    Lymphopenia 1/60 (1.7%) 6/64 (9.4%) 5/64 (7.8%)
    Neutropenia 24/60 (40%) 43/64 (67.2%) 44/64 (68.8%)
    Thrombocytopenia 8/60 (13.3%) 18/64 (28.1%) 34/64 (53.1%)
    Cardiac disorders
    Tachycardia 3/60 (5%) 1/64 (1.6%) 3/64 (4.7%)
    Eye disorders
    Lacrimation increased 1/60 (1.7%) 4/64 (6.3%) 1/64 (1.6%)
    Vision blurred 3/60 (5%) 0/64 (0%) 1/64 (1.6%)
    Gastrointestinal disorders
    Abdominal pain 4/60 (6.7%) 9/64 (14.1%) 5/64 (7.8%)
    Abdominal pain upper 5/60 (8.3%) 7/64 (10.9%) 5/64 (7.8%)
    Constipation 13/60 (21.7%) 27/64 (42.2%) 25/64 (39.1%)
    Diarrhoea 25/60 (41.7%) 26/64 (40.6%) 13/64 (20.3%)
    Dry mouth 3/60 (5%) 2/64 (3.1%) 1/64 (1.6%)
    Dyspepsia 3/60 (5%) 2/64 (3.1%) 4/64 (6.3%)
    Gastrooesophageal reflux disease 3/60 (5%) 1/64 (1.6%) 1/64 (1.6%)
    Nausea 26/60 (43.3%) 34/64 (53.1%) 27/64 (42.2%)
    Stomatitis 5/60 (8.3%) 14/64 (21.9%) 8/64 (12.5%)
    Vomiting 18/60 (30%) 13/64 (20.3%) 11/64 (17.2%)
    General disorders
    Asthenia 13/60 (21.7%) 10/64 (15.6%) 15/64 (23.4%)
    Chills 4/60 (6.7%) 3/64 (4.7%) 2/64 (3.1%)
    Fatigue 33/60 (55%) 32/64 (50%) 24/64 (37.5%)
    Generalised oedema 3/60 (5%) 0/64 (0%) 0/64 (0%)
    Influenza like illness 3/60 (5%) 4/64 (6.3%) 2/64 (3.1%)
    Non-cardiac chest pain 6/60 (10%) 3/64 (4.7%) 2/64 (3.1%)
    Oedema peripheral 17/60 (28.3%) 12/64 (18.8%) 10/64 (15.6%)
    Pain 3/60 (5%) 3/64 (4.7%) 6/64 (9.4%)
    Pyrexia 12/60 (20%) 5/64 (7.8%) 8/64 (12.5%)
    Immune system disorders
    Drug hypersensitivity 3/60 (5%) 9/64 (14.1%) 2/64 (3.1%)
    Hypersensitivity 0/60 (0%) 5/64 (7.8%) 0/64 (0%)
    Infections and infestations
    Bronchitis 2/60 (3.3%) 5/64 (7.8%) 1/64 (1.6%)
    Cellulitis 4/60 (6.7%) 2/64 (3.1%) 0/64 (0%)
    Folliculitis 4/60 (6.7%) 1/64 (1.6%) 0/64 (0%)
    Influenza 1/60 (1.7%) 4/64 (6.3%) 2/64 (3.1%)
    Sinusitis 3/60 (5%) 2/64 (3.1%) 0/64 (0%)
    Upper respiratory tract infection 6/60 (10%) 7/64 (10.9%) 2/64 (3.1%)
    Urinary tract infection 3/60 (5%) 11/64 (17.2%) 6/64 (9.4%)
    Injury, poisoning and procedural complications
    Contusion 1/60 (1.7%) 5/64 (7.8%) 1/64 (1.6%)
    Fall 4/60 (6.7%) 5/64 (7.8%) 1/64 (1.6%)
    Overdose 1/60 (1.7%) 6/64 (9.4%) 2/64 (3.1%)
    Investigations
    Alanine aminotransferase increased 6/60 (10%) 0/64 (0%) 5/64 (7.8%)
    Aspartate aminotransferase increased 6/60 (10%) 0/64 (0%) 4/64 (6.3%)
    Weight decreased 8/60 (13.3%) 4/64 (6.3%) 3/64 (4.7%)
    Metabolism and nutrition disorders
    Decreased appetite 15/60 (25%) 14/64 (21.9%) 10/64 (15.6%)
    Dehydration 6/60 (10%) 1/64 (1.6%) 3/64 (4.7%)
    Hyperglycaemia 4/60 (6.7%) 5/64 (7.8%) 2/64 (3.1%)
    Hypokalaemia 8/60 (13.3%) 12/64 (18.8%) 7/64 (10.9%)
    Hypomagnesaemia 1/60 (1.7%) 12/64 (18.8%) 5/64 (7.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 13/60 (21.7%) 9/64 (14.1%) 7/64 (10.9%)
    Back pain 3/60 (5%) 14/64 (21.9%) 6/64 (9.4%)
    Bone pain 7/60 (11.7%) 5/64 (7.8%) 8/64 (12.5%)
    Muscular weakness 1/60 (1.7%) 2/64 (3.1%) 4/64 (6.3%)
    Musculoskeletal chest pain 3/60 (5%) 3/64 (4.7%) 3/64 (4.7%)
    Musculoskeletal pain 1/60 (1.7%) 2/64 (3.1%) 4/64 (6.3%)
    Myalgia 14/60 (23.3%) 14/64 (21.9%) 4/64 (6.3%)
    Neck pain 3/60 (5%) 3/64 (4.7%) 4/64 (6.3%)
    Pain in extremity 8/60 (13.3%) 7/64 (10.9%) 4/64 (6.3%)
    Spinal pain 3/60 (5%) 1/64 (1.6%) 0/64 (0%)
    Nervous system disorders
    Dizziness 3/60 (5%) 11/64 (17.2%) 9/64 (14.1%)
    Dysgeusia 9/60 (15%) 9/64 (14.1%) 4/64 (6.3%)
    Headache 17/60 (28.3%) 14/64 (21.9%) 12/64 (18.8%)
    Hypoaesthesia 2/60 (3.3%) 4/64 (6.3%) 2/64 (3.1%)
    Neuropathy peripheral 4/60 (6.7%) 11/64 (17.2%) 3/64 (4.7%)
    Neurotoxicity 4/60 (6.7%) 3/64 (4.7%) 0/64 (0%)
    Paraesthesia 4/60 (6.7%) 7/64 (10.9%) 2/64 (3.1%)
    Peripheral sensory neuropathy 14/60 (23.3%) 14/64 (21.9%) 5/64 (7.8%)
    Psychiatric disorders
    Anxiety 3/60 (5%) 2/64 (3.1%) 3/64 (4.7%)
    Depression 4/60 (6.7%) 2/64 (3.1%) 7/64 (10.9%)
    Insomnia 8/60 (13.3%) 12/64 (18.8%) 11/64 (17.2%)
    Reproductive system and breast disorders
    Breast pain 0/60 (0%) 2/64 (3.1%) 5/64 (7.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 12/60 (20%) 17/64 (26.6%) 7/64 (10.9%)
    Dyspnoea 7/60 (11.7%) 15/64 (23.4%) 11/64 (17.2%)
    Dyspnoea exertional 2/60 (3.3%) 4/64 (6.3%) 1/64 (1.6%)
    Epistaxis 3/60 (5%) 5/64 (7.8%) 2/64 (3.1%)
    Nasal congestion 0/60 (0%) 6/64 (9.4%) 1/64 (1.6%)
    Oropharyngeal pain 4/60 (6.7%) 5/64 (7.8%) 0/64 (0%)
    Pleural effusion 5/60 (8.3%) 2/64 (3.1%) 1/64 (1.6%)
    Rhinorrhoea 3/60 (5%) 2/64 (3.1%) 1/64 (1.6%)
    Skin and subcutaneous tissue disorders
    Alopecia 33/60 (55%) 25/64 (39.1%) 7/64 (10.9%)
    Dry skin 3/60 (5%) 1/64 (1.6%) 0/64 (0%)
    Erythema 4/60 (6.7%) 5/64 (7.8%) 3/64 (4.7%)
    Pruritus 5/60 (8.3%) 9/64 (14.1%) 4/64 (6.3%)
    Rash 8/60 (13.3%) 3/64 (4.7%) 2/64 (3.1%)
    Rash maculo-papular 3/60 (5%) 0/64 (0%) 0/64 (0%)
    Rash pruritic 3/60 (5%) 1/64 (1.6%) 1/64 (1.6%)
    Vascular disorders
    Deep vein thrombosis 1/60 (1.7%) 0/64 (0%) 4/64 (6.3%)
    Hot flush 4/60 (6.7%) 5/64 (7.8%) 2/64 (3.1%)
    Hypertension 8/60 (13.3%) 4/64 (6.3%) 1/64 (1.6%)
    Lymphoedema 2/60 (3.3%) 6/64 (9.4%) 3/64 (4.7%)

    Limitations/Caveats

    Due to changes in the treatment landscape since the trial initiation, including the initiation of trials with immunotherapy drugs, successful enrollment of the Phase 3 part was considered unlikely and was not conducted; no safety signals were raised.

    More Information

    Certain Agreements

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

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 12 months since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for 90 more days. Investigator must delete confidential information before submission or defer publication to permit patent applications.

    Results Point of Contact

    Name/Title Anne McClain, Senior Manager Clinical Trial Disclosure
    Organization Celgene
    Phone 888-260-1599
    Email ClinicalTrialDisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01881230
    Other Study ID Numbers:
    • ABI-007-MBC-001
    • 2013-000113-20
    First Posted:
    Jun 19, 2013
    Last Update Posted:
    Feb 21, 2019
    Last Verified:
    Feb 1, 2019