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A Phase 2/3, Multi-center, Open-label, Randomized Study of Weekly Nab-paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to the Combination of Gemcitabine and Carboplatin, as First-line Treatment in Female Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer

Phase 2/Phase 3
18 Years
Not Enrolling
Breast Tumors,, Breast Cancer,, Cancer of the Breast,, Human Mammary Carcinoma,, Mammary Carcinoma, Human;, Mammary Neoplasms, Human;, Tumors, Breast;, Neoplasms, Breast

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Trial Information

A Phase 2/3, Multi-center, Open-label, Randomized Study of Weekly Nab-paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to the Combination of Gemcitabine and Carboplatin, as First-line Treatment in Female Subjects With ER, PgR, and HER2 Negative (Triple Negative) Metastatic Breast Cancer

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. 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.

Inclusion Criteria:

- 1. Female subjects, 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 Flourescence 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

- 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 Cockroft-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;

- 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 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

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

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

6. Serious intercurrent medical or psychiatric illness, including serious active

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, idopathic
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

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS) (Phase 2)

Outcome Description:

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)

Outcome Time Frame:

Up to approximately 18 months

Safety Issue:


Principal Investigator

Debora Barton, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Celgene Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

June 2013

Completion Date:

June 2019

Related Keywords:

  • Breast Tumors,
  • Breast Cancer,
  • Cancer of the Breast,
  • Human Mammary Carcinoma,
  • Mammary Carcinoma, Human;
  • Mammary Neoplasms, Human;
  • Tumors, Breast;
  • Neoplasms, Breast
  • Breast Cancer,
  • Cancer of the Breast,
  • Metastatic Breast Cancer,
  • Triple negative breast cancer,
  • triple negative metastatic breast cancer,
  • basal- like breast cancer,
  • hormone receptor negative breast cancer,
  • Abraxane,
  • nab-paclitaxel,
  • ABI007,
  • gemcitabine,
  • Gemzar,
  • carboplatin,
  • Paraplatin,
  • Paraplatin AQ,
  • Phase 2,
  • Phase 3
  • Breast Neoplasms
  • Mammary Neoplasms, Animal
  • Neoplasms
  • Carcinoma