Clinical study for patients with breast cancer that has spread to other parts of the body and that does not respond to hormonal or anti-HER2 therapy ('triple negative disease'), comparing a chemotherapy treatment (carboplatin + gemcitabine) with an experimental treatment of nab-paclitaxel plus chemotherapy (carboplatin OR gemcitabine).

• Register: EUCTR
• Last refreshed on: 5 December 2016
• Main ID: EUCTR2013-000113-20-GR
• Date of registration: 01/10/2013
• Prospective Registration: Yes
• Primary sponsor: Abraxis BioScience, LLC, a wholly-owned subsidiary of Celgene Corporation
• Public title: Clinical study for patients with breast cancer that has spread to other parts of the body and that does not respond to hormonal or anti-HER2 therapy ('triple negative disease'), comparing a chemotherapy treatment (carboplatin + gemcitabine) with an experimental treatment of nab-paclitaxel plus chemotherapy (carboplatin OR gemcitabine).
• 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 - TNACITY
• Date of first enrolment: 05/12/2013
• Target sample size: 790
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000113-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: carboplatin + gemcitabine Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Brazil, Canada, France, Germany, Greece, Italy, Japan, Portugal, Spain, United Kingdom, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion 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 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. 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 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.

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. ECOG performance status 0–1

11. Subject has the following blood counts at screening:
- ANC = 1500/mm2 ;
- platelets = 100,000/mm2 ;
- Hemoglobin = 9 g/dL

12. Subject has the following blood chemistry levels at screening:
- AST (SGOT), ALT (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 Cockroft-Gault)

13. Females of child-bearing potential [defined as a sexually mature woman 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
Exclusion criteria:
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 treatment

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 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, idopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies

10. Peripheral neuropathy Grade = 2 by 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 IP are eligible.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

ER, PgR, and HER2 negative (triple negative) metastatic breast cancer
MedDRA version: 14.1 Level: HLT Classification code 10006289 Term: Benign and malignant breast neoplasms System Organ Class: 100000004872
MedDRA version: 14.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Abraxane

Product Code: nab-paclitaxel, ABI-007
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Current Sponsor code: ABI-007
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Carboplatin 10mg/ml concentrate for solution for infusion
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Gemcitabine for Injection 1g

Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Primary end point(s): Phase II: Progression-Free Survival (PFS) based on investigator assessment of response using RECIST 1.1 guidelines.

Phase III: Progression-Free Survival (PFS) based on an independent blinded radiologist(s) assessment using RECIST 1.1 guidelines.

Main Objective: - Phase 2: evaluate the benefit and risk profiles of the two nab-paclitaxel experimental arms and identify the nab-paclitaxel combination that will be used in the Phase 3.

- Phase 3: compare the progression-free survival (PFS) of nab-paclitaxel plus either gemcitabine or carboplatin to gemcitabine/carboplatin in subjects with TNMBC, as assessed by independent blinded radiologist(s) using RECIST 1.1 guidelines.

Timepoint(s) of evaluation of this end point: - in phase II: when approximately 144 PFS events have ocurred

- in phase III: when 330 PFS events or 217 deaths have ocurred, whichever is later

Secondary Objective: - Phase 2:
? safety
? investigator-determined progression free survival (PFS)
? investigator-determined overall response rate (ORR)
? Overall survival (OS)

- Phase 3:
? Compare safety and tolerability of each treatment regimen
? Compare Overall Response Rate (ORR), determined by independent blinded radiologist(s)
? Compare Overall Survival (OS)
? Compare Disease Control Rate (CR, PR and SD = 16 weeks)
? Compare Duration of Response

Secondary Outcome(s)

Secondary end point(s): - phase II:
? Efficacy: Overall Response Rate (ORR), investigator-determined, using RECIST 1.1 guidelines; percentage of subjects who initiated Cycle 6; overall Survival
? Safety: Incidence/Grade of TEAEs, serious adverse events (SAEs), laboratory abnormalities; incidence of subjects experiencing dose modifications (dose interruptions and
reductions); percentage of subjects who discontinued for adverse event

- Phase III:
key secondary endpoints: ORR with a confirmed complete or partial response; OS;
others: efficacy (investigator assessment of PFS; disease control rate; duration of response in subjects with objective CR or PR), safety (incidence of TEAEs, SAEs, laboratory abnormalities)

Timepoint(s) of evaluation of this end point: phase II: efficacy and safety at cut-off date of follow-up period

phase III: efficacy and safety at cut-off date of follow-up period; final analysis of overall survival after approximately 309 deaths

Secondary ID(s)

2013-000113-20-AT

ABI-007-MBC-001

Source(s) of Monetary Support

Celgene Corporation