A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients with Early Relapsing Recurrent Triple-Negative Breast Cancer

• Register: EUCTR
• Last refreshed on: 19 February 2024
• Main ID: EUCTR2016-005119-42-FI
• Date of registration: 16/05/2018
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients with Early Relapsing Recurrent Triple-Negative Breast Cancer
• Scientific title: A PHASE III, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTRE STUDY OF THE EFFICACY AND SAFETY OF ATEZOLIZUMAB PLUS CHEMOTHERAPY FOR PATIENTS WITH EARLY RELAPSING RECURRENT (INOPERABLE LOCALLY ADVANCED OR METASTATIC) TRIPLE-NEGATIVE BREAST CANCER
• Date of first enrolment: 22/05/2018
• Target sample size: 597
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-005119-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Bosnia and Herzegovina, Brazil, Cuba, Egypt, Finland, France, Germany, Hong Kong, Hungary, Italy, Kazakhstan, Korea, Republic of, Mexico, Morocco, Panama, Poland, Portugal, Russian Federation, Serbia, Singapore, South Africa, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female >= 18 years of age
- Histologically confirmed TNBC that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
- Prior treatment with an anthracycline and taxane
- Documented disease progression occurring within 12 months (<12 months) from the last treatment with curative intent
- Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. China Population only: Chinese traditional medicines with an approved indication for cancer treatment are permitted as long as the last administration occurred at least 2 weeks prior to randomisation
- Measurable or non-measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Availability of a representative formalin-fixed paraffin-embedded
(FFPE) tumour block (preferred) or at least 17 unstained slides, obtained
from relapsed metastatic or locally advanced diseases may be submitted,
if clinically feasible, with an associated pathology report, if available If a
fresh tumour is not clinically feasible, either the diagnosis sample, the
primary surgical resection sample or the most recent FFPE tumour
biopsy sample should be used
- Eastern Cooperative Oncology Group performance status 0-1
- Life expectancy >= 12 weeks
- Adequate haematologic and end-organ function, Negative human immunodeficiency virus (HIV) test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- The HCV RNA test will be performed only for patients who have a negative HBsAg test and a positive HCV antibody test
- For women of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use a contraceptive method
with a failure rate of <=1% per year during the treatment period and for
5 months after the final dose of atezo or 6 months after the last dose of
capecitabine. Women must refrain from donating eggs during the same
time period
- For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agreement to refrain from donating
sperm, with female partners of childbearing potential or pregnant female
partners, men must remain abstinent or use a condom during the
treatment period and for at least 3 months after last dose of
capecitabine or 6 months after the last dose of carboplatin/gemcitabine
to avoid exposing the embryo.
-For patients enrolled after the recruitment of all-comers is complete: PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells of 1% or greater.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 508
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 89

Exclusion criteria:
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomisation
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Symptomatic or rapid visceral progression
- History of leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumour-related pain
- Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Malignancies other than TNBC within 5 years prior to randomisation, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer)
- Significant cardiovascular disease
- Presence of an abnormal ECG that is clinically significant in the investigator’s opinion
- Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia
- Current treatment with anti-viral therapy for HBV
- Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
- Treatment with investigational therapy within 28 days prior to randomisation
- Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of study treatment atezo, or within 6 months after the last dose of capecitabine, whichever is later
- History of autoimmune disease
- History of idiopathic pulmonary fibrosis (including pneumonitis), druginduced
pneumonitis, organizing pneumonia (i.e., bronchiolitis
obliterans, cryptogenic organizing pneumonia), or evidence of active
pneumonitis on screening chest computerised tomography (CT) scan
-Receipt of a live, attenuated vaccine within 4 weeks prior to
randomisation or anticipation that a live, attenuated vaccine will be
required during atezolizumab/placebo treatment or within 5 months
after the last dose of atezolizumab/placebo
-Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1
therapeutic antibody or pathway targeting agents
-Treatment with systemic immunostimulatory agents (including but not
limited to interferons or interleukin [IL]-2) within 4 weeks or five halflives
of the drug (whichever is longer) prior to randomisation
-Treatment with systemic corticosteroids or other systemic
immunosuppressive medications (including but not limited to
prednisone, dexamethasone, cyclophosphamide, azathioprine,
methotrexate, thalidomide, mycophenolate, and anti tumour necrosis
factor [TNF] agents) within 2 weeks prior to initiation of study
treatment, or anticipated requirement for systemic immunosuppressive
medications during the trial.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Triple-Negative Breast Cancer (TNBC)
MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Product Name: atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Carbosin
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: carboplatin
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Xeloda
Product Name: Capecitabine
Product Code: RO 0091978
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CAPECITABINE
Current Sponsor code: Ro 009-1978/J12-00
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
INN or Proposed INN: CAPECITABINE
Current Sponsor code: Ro009-1978/J13-00
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Gitrabin 200mg
Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 38-

Trade Name: Gitrabin 1000mg
Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 38-

Trade Name: Tecentriq
Product Name: atezolizumab
Product Code: R

Primary Outcome(s)

Main Objective: • To evaluate the efficacy of atezolizumab (atezo) (+) chemotherapy compared to placebo + chemotherapy based on overall survival

Secondary Objective: To Evaluate:
• Efficacy of atezo + chemotherapy compared to placebo +
chemotherapy based on survival rate, progression free survival,
objective response rate (ORR), duration of objective response (DoR),
clinical benefit rate, confirmed-ORR, confirmed DoR
• Patient-reported outcomes (PROs) of global health status (GHS)/
quality of life (QoL) associated with atezolizumab + chemotherapy
compared with chemotherapy alone, as measured by European
Organization for Research and Treatment of Cancer Quality of Life
Questionnaire Core 30 (EORTC QLQ-C30)
• Safety of atezo + chemotherapy compared with placebo +
chemotherapy
• Pharmacokinetics (PK) of atezo when administered with
carboplatin/gemcitabine or with capecitabine in patients with breast
cancer
• Immunogenicity of atezo
• Efficacy, safety of atezo + chemotherapy according to programmed
death-ligand 1 (PD-L1) status
•Consistency in efficacy between China and the Global population (atezo
+ chemotherapy compared with placebo + chemotherapy)

Primary end point(s): 1. Overall survival in the population with PD-L1-positive tumour status
and then if statistically significant, in the modified intent-to-treat (mITT)
population.

Timepoint(s) of evaluation of this end point: 1. Up to 58 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Month 12
2. Month 18
3-15. Up to 58 months

Secondary end point(s): 1. 12-month survival rate
2. 18-month survival rate
3. Progression-free survival in the PD-L1-positive population, and then if
statistically significant in the mITT population
4. ORR in the PD-L1-positive population, and then if statistically
significant in the mITT population
5. DoR
6. Clinical benefit rate
7. Confirmed ORR
8. Confirmed DoR
9. Time to confirmed deterioration (TTD) of GHS/QoL
10. Incidence, nature and severity of adverse events (AEs), with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0)
11. Change from baseline in targeted vital signs and physical findings
12. Change from baseline in targeted clinical laboratory test results
13. Maximum and minimum observed serum concentration (Cmax and Cmin) of atezolizumab
14. Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline.
15. Relationship between PD-L1 protein expression by immunohistochemistry (Ventana® PD-L1 SP142 IHC assay) in screening tumour tissue and clinical outcomes

Secondary ID(s)

MO39193

2016-005119-42-HU

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 15/05/2018
Contact: