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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01881230
First received: June 17, 2013
Last updated: June 16, 2014
Last verified: June 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) or metastatic triple negative breast cancer.


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) (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 subjects who initiated Cycle 6 receiving doublet combination therapy (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

  • 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 Percentage and number of subjects who discontinued for adverse event

  • Independent blinded radiologists-determined Overall Response Rate (ORR) (Phase 3) [ Time Frame: Up to approximately 46 months ] [ Designated as safety issue: No ]
    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 objective 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 ]
    PFS is defined as the number of subjects who survive without progressing

  • Incidence of subjects experiencing dose modifications (dose interruptions and reductions); [ Time Frame: Up to 19 months ] [ Designated as safety issue: Yes ]
    The number of subjects with dose interruptions and reductions experienced by participants that occurred during the treatment period. Dose interruptions and reductions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

  • Percentage of subjects who discontinued from all study treatment adverse event [ Time Frame: Up to 19 months ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values (as specified by the criteria below), regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE


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/m^2 plus gemcitabine 1000mg/m^2
(Phase 2) Treatment Arm A: nab-Paclitaxel 125mg/m^2 on Days 1 and 8 by intravenousI (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/m^2 plus carboplatin AUC2
(Phase 2) Treatment Arm B: nab-Paclitaxel 125 mg/m^2 on Days 1 and 8 by IV administration without hypersensitivity prophylaxis, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration
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/m^2 plus carboplatin AUC2
(Phase 2) Treatment Arm C: Gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration followed by carboplatin AUC2 on Days 1 and 8 by IV administration
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 without hypersensitivity prophylaxis, followed by gemcitabine 1000 mg/m2 on Days 1 and 8 by IV administration OR nab-Paclitaxel 125 mg/m2 on Days 1 and 8 by IV administration without hypersensitivity prophylaxis, followed by carboplatin AUC 2 on Days 1 and 8 by IV administration
Drug: Carboplatin AUC 2
Other Names:
  • Paraplatin,
  • Paraplatin AQ
Drug: gemcitabine 1000 mg
Other Name: Gemzar
Active Comparator: Gemcitabine 1000mg/m^2 plus carboplatin AUC 2
(Phase 3) Treatment Arm 2: Gemcitabine 1000 mg/m^2 on Days 1 and 8 by IV administration over 30 minutes, followed by carboplatin AUC2 on Days 1 and 8 by IV administration
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
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, see Learn About Clinical Studies.

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 133 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: June 16, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Brazil: Ministry of Health
Canada: Health Canada
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
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
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
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
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 18, 2014