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

This study is currently recruiting participants.
Verified April 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01881230
First received: June 17, 2013
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention 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 125 mg/m2 plus carboplatin AUC 2 in triple negative metastatic breast cancer (TNMBC) subjects
Drug: Carboplatin AUC 2
Drug: gemcitabine 1000 mg
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Progression Free Survival (PFS) for triple negative metastatic breast cancer subjects (Phase 2) [ Time Frame: Up to approximately 18 months ] [ Designated as safety issue: No ]
    time from the randomization date to the start of disease progression or subject death from any cause (progression assessed by investigator using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1 guidelines) for triple negative metastatic breast cancer (TNMBC) subjects

  • Progression Free Survival (PFS) for triple negative metastatic breast cancer subjects (Phase 3) [ Time Frame: Up to approximately 46 months ] [ Designated as safety issue: No ]
    Time from the randomization date to the start of disease progression or subject death from any cause (assessment based on an independent blinded radiologist(s) evaluation using RECIST 1.1 guidelines for triple negative metastatic breast cancer (TNMBC) subjects


Secondary Outcome Measures:
  • Investigator-determined Overall Response Rate (ORR) for triple negative metastatic breast cancer subjects (Phase 2) [ Time Frame: Up to approximately 18 months ] [ Designated as safety issue: No ]
    Complete response (CR) or partial response (PR) based on investigator assessment of response using RECIST 1.1 guidelines

  • Percentage of triple negative metastatic breast cancer subjects who initiated Cycle 6 (Phase 2) [ Time Frame: Up to approximately 18 months ] [ Designated as safety issue: No ]
    Defined as the Percentage of subjects who initiated Cycle 6 of treatment regardless of the need for dose modifications

  • Investigator determined Overall Survival (OS) for triple negative metastatic breast cancer (TNMBC) subjects (Phase 2) [ Time Frame: Up to approximately 18 months ] [ Designated as safety issue: No ]
    Defined as the time between randomization and death

  • Safety for triple negative metastatic breast cancer (TNMBC) subjects (Phase 2) [ Time Frame: up to approximately 19 months ] [ Designated as safety issue: Yes ]
    Incidence/Grade of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), laboratory abnormalities; Incidence of subjects experiencing dose modifications (dose interruptions and reductions); Percentage and number of subjects who discontinued for adverse event

  • Independent blinded radiologists-determined Overall Response Rate (ORR) for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: Up to approximately 46 months ] [ Designated as safety issue: No ]
    Confirmed complete or partial response according to RECIST 1.1 guidelines determined by independent, blinded radiologist(s)

  • Overall Survival (OS) for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: Up to approximately 66 months ] [ Designated as safety issue: No ]
    Time between randomization and death

  • Compare disease control rate for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: Up to approximately 46 months ] [ Designated as safety issue: No ]
    Complete response (CR), Partial response (PR), and Stable Disease (SD) more than or equal to 16 weeks for triple negative metastatic breast cancer (TNMBC) subjects

  • Duration of Response for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: Up to approximately 46 months ] [ Designated as safety issue: No ]
    period from confirmed complete or partial response (whichever is first recorded) until the first date that progression free survival event is documented

  • Safety of each treatment regimen for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: Up to approximately 47 months ] [ Designated as safety issue: Yes ]
    : Assessment based on Adverse Events (AEs) , Serious Adverse Events (SAEs), laboratory abnormalities in triple negative metastatic breast cancer (TNMBC) subjects .

  • Investigator assessed Progression Free Survival (PFS)for triple negative metastatic breast cancer (TNMBC) subjects (Phase 3) [ Time Frame: up to approximately 46 months ] [ Designated as safety issue: No ]
    Assessment based on investigator evaluation using RECIST 1.1 guidelines


Estimated Enrollment: 790
Study Start Date: June 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nab-Paclitaxel 125mg/m2 plus gemcitabine 1000mg/m2 in TNMBC
Treatment Arm A: nab-Paclitaxel 125mg/m2 on Days 1 and 8 by IV administration over 30 minutes, followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes in triple negative metastatic breast cancer (TNMBC) subjects
Drug: gemcitabine 1000 mg
Other Name: Gemzar
Experimental: nab-Paclitaxel 125mg/m2 plus carboplatin AUC2 in TNMBC
Treatment Arm B: nab-Paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes followed by carboplatin AUC 2 on Days 1 and 8 by IV administration over 60 minutes
Drug: nab-Paclitaxel 125 mg/m2 plus carboplatin AUC 2 in triple negative metastatic breast cancer (TNMBC) subjects
Other Name: Abraxane
Drug: Carboplatin AUC 2
Other Names:
  • Paraplatin,
  • Paraplatin AQ
Active Comparator: Gemcitabine 1000mg/m2 plus carboplatin AUC2
Treatment Arm C: Gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes, followed by carboplatin AUC2 on Days 1 and 8 by IV administration over 60 minutes in triple negative metastatic breast cancer (TNMBC) subjects
Drug: Carboplatin AUC 2
Other Names:
  • Paraplatin,
  • Paraplatin AQ
Drug: gemcitabine 1000 mg
Other Name: Gemzar
Experimental: Selected nab Paclitaxel arm from Phase 2 inTNMBC subjects
Phase 3 Treatment Arm 1: Selected Phase 2 nab paclitaxel treatment arm of either nab-Paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes OR nab-Paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration over 30 minutes followed by carboplatin AUC 2 on Days 1 and 8 by IV administration over 60 minutes in triple negative metastatic breast cancer (TNMBC) subjects
Drug: Carboplatin AUC 2
Other Names:
  • Paraplatin,
  • Paraplatin AQ
Drug: gemcitabine 1000 mg
Other Name: Gemzar
Active Comparator: Phase 3: Gemcitabine plus carboplatin
Phase 3 Treatment Arm 2: Gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration over 30 minutes, followed by carboplatin AUC2 on Days 1 and 8 by IV administration over 60 minutes in triple negative metastatic breast cancer (TNMBC) subjects
Drug: Carboplatin AUC 2
Other Names:
  • Paraplatin,
  • Paraplatin AQ
Drug: gemcitabine 1000 mg
Other Name: Gemzar

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 either 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). 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 triple negative metastatic breast cancer (TNMBC) subjects.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Female subjects with triple negative metastatic breast cancer, age 18 years or older at the time informed consent is signed 2. Pathologically confirmed metastatic adenocarcinoma of the breast

    a. Paraffin fixed primary or metastatic site tumor sample (most recently obtained) is required for central laboratory biomarker evaluation 3. Pathologically confirmed as triple negative, source documented, defined as both of the following

    a. 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) (Hammond, 2010) b. Human Epidermal Growth Factor Receptor 2(HER2) negative (Wolff, 2007): i. Immunohistochemistry (IHC) 0 or 1+, or ii. IHC 2+ and confirmed negative by Fluorescence In Situ Hybridization (FISH), (FISH HER2/CEP17 ratio < 1.8), or iii. Average HER2 gene copy number of < 4 signals/nucleus for test systems without and internal control probe 4. Subjects must have received prior adjuvant or neoadjuvant anthracycline therapy; or anthracycline treatment must be clinically contraindicated.

    5. Subjects with measurable disease, defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) guidelines 6. 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.

    7. Prior neoadjuvant or adjuvant chemotherapy, if given, must have been completed at least 30 days before start of study treatment with all related toxicities resolved, and documented evidence of disease progression per RECIST 1.1 guidelines is required 8. Prior radiotherapy must have completed at least 2 weeks before randomization, with full recovery. The measurable disease (target lesions) must be completely outside the radiation portal or there must be unequivocal radiologic or clinical exam proof of progressive disease within the radiation portal 9. At least 30 days from major surgery before the start of study treatment, with full recovery 10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 11. Subject has the following blood counts at screening:

    • Absolute Neutrophil Count (ANC) ≥ 1500/mm2 ;
    • platelets ≥ 100,000/mm2 ;
    • Hemoglobin (Hgb) ≥ 9 g/dL 12. 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 bilirubin ≤ ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN)
    • alkaline phosphatase ≤ 2.5 x ULN (unless bone metastases are present in the absence of liver metastasis)
    • creatinine clearance > 60 mL/min (by Cockcroft-Gault) 13. 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:
    • Agree to the use of two physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study medication; and for 28 days following the last dose of study medication; and
    • 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 14. Females must abstain from breastfeeding during study participation and 28 days after investigational product discontinuation 15. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted 16. 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 with triple negative metastatic breast cancer.
    2. Concurrent chemotherapy or any other anti tumor therapy for breast cancer. Prior immunotherapy & monoclonal antibody therapy are acceptable.
    3. Concurrent or prior anticoagulation therapy within 7 days of first dose of study treatment
    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. Serious intercurrent medical or psychiatric illness, including serious active infection
    7. History of class II-IV congestive heart failure or myocardial infarction within 6 months of beginning study treatment
    8. History of other primary malignancy in the last 5 years. Subjects with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years
    9. 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 allergies
    10. Peripheral neuropathy Grade ≥ 2 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
    11. Subjects who have received an investigational product within the previous 4 weeks prior to study randomization
    12. 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
    13. Pregnant or nursing women
    14. Subjects with prior hypersensitivity to nab-paclitaxel, gemcitabine, carboplatin or any other platin, or nucleoside analogue agents
    15. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
    16. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if she were to participate in the study
    17. Any condition that confounds the ability to interpret data from the study
    18. History of seropositive human immunodeficiency virus (HIV) or subjects who are receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications
    19. Initiation of bisphosphonate for bone metastasis therapy while on study. Subjects receiving bisphosphonate therapy initiated ≥ 1 day prior to starting investigational product are eligible.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01881230

Contacts
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

  Show 131 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Debora Barton, M.D. Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01881230     History of Changes
Other Study ID Numbers: ABI-007-MBC-001, 2013-000113-20
Study First Received: June 17, 2013
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Brazil: Ministry of Health
Canada: Health Canada
Finland: Finnish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Metastatic Breast Cancer
Triple Negative Metastatic Breast Cancer
Hormone receptor negative
HER2 Negative
Abraxane
nab-Paclitaxel
gemcitabine
carboplatin
TNMBC

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 16, 2014