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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) (tnAcity)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01881230
Recruitment Status : Completed
First Posted : June 19, 2013
Results First Posted : March 8, 2018
Last Update Posted : February 21, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Description
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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
Breast Tumor Breast Cancer Cancer of the Breast Estrogen Receptor- Negative Breast Cancer HER2- Negative Breast Cancer Progesterone Receptor- Negative Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Triple-negative Breast Cancer Triple-negative Metastatic Breast Cancer Metastatic Breast Cancer Drug: nab-Paclitaxel Drug: Carboplatin Drug: Gemcitabine 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
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Study Type : Interventional  (Clinical Trial)
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 : September 26, 2013
Actual Primary Completion Date : October 28, 2016
Actual Study Completion Date : October 28, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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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 Name: Abraxane

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


Outcome Measures
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Primary Outcome Measures :
  1. Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment. [ 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 ]
    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. [ 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 ]
    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 [ Time Frame: 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 [ 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 ]
    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) [ 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 ]
    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) [ 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 ]
    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 [ 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 ]
    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
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

    1. 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)
    2. 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).
  4. 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

  5. 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.

    a. 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.

  6. Subjects with measurable metastatic disease, defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines
  7. Life expectancy ≥ 16 weeks from randomization
  8. 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.

  9. 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.

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

  10. 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
  11. At least 30 days from major surgery before randomization, with full recovery
  12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

  13. 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

  14. 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)

  15. 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
  16. 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
  17. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted
  18. 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01881230


Locations
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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Ileana Elias, M.D. Celgene Corporation
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01881230    
Other Study ID Numbers: ABI-007-MBC-001
2013-000113-20 ( EudraCT Number )
First Posted: June 19, 2013    Key Record Dates
Results First Posted: March 8, 2018
Last Update Posted: February 21, 2019
Last Verified: February 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:
Layout table for MeSH terms
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Carboplatin
Gemcitabine
 Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites