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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01881230




Registration number
NCT01881230
Ethics application status
Date submitted
17/06/2013
Date registered
19/06/2013
Date last updated
21/02/2019

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2013-000113-20
Secondary ID [2] 0 0
ABI-007-MBC-001
Universal Trial Number (UTN)
Trial acronym
tnAcity
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Tumor 0 0
Breast Cancer 0 0
Cancer of the Breast 0 0
Estrogen Receptor- Negative Breast Cancer 0 0
HER2- Negative Breast Cancer 0 0
Progesterone Receptor- Negative Breast Cancer 0 0
Recurrent Breast Cancer 0 0
Stage IV Breast Cancer 0 0
Triple-negative Breast Cancer 0 0
Triple-negative Metastatic Breast Cancer 0 0
Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - nab-Paclitaxel
Treatment: Drugs - Carboplatin
Treatment: Drugs - Gemcitabine

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

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

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


Treatment: Drugs: 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.

Treatment: Drugs: Carboplatin
Carboplatin at an AUC of 2 on Days 1 and 8 of each 21-day cycle by IV administration

Treatment: Drugs: Gemcitabine
Gemcitabine 1000 mg/m\^2 on Days 1 and 8 of each 21-day treatment cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.
Timepoint [1] 0 0
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
Secondary outcome [1] 0 0
Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy
Timepoint [2] 0 0
Cycle 6
Secondary outcome [3] 0 0
Kaplan-Meier Estimates of Overall Survival
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs
Timepoint [6] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/10/2016
Sample size
Target
Accrual to date
Final
191
Recruitment in Australia
Recruitment state(s)
ACT,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Frankston Hospital Oncology Research - Frankston
Recruitment hospital [3] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
3690 - Wodonga
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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California
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Florida
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Illinois
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Indiana
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Louisiana
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Genova
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Grosseto
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Messina
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Monza
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Napoli, Campania
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Padova
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Roma
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Torino, Piemonte
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Treviglio
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Evora
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Sevilla
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Bath
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London
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Manchester
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Middlesex
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United Kingdom
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Sheffield South Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ileana Elias, M.D.
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01881230