A phase Ib/II study of Durvalumab (MEDI4736) combined with dose-dense EC in a neoadjuvant setting for patients with locally advanced luminal B HER2(-) or triple negative breast cancers (B-IMMUNE)
- Conditions
- patients with locally advanced luminal B HER2(-) or triple negative breast cancers (B-IMMUNE)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003998-17-BE
- Lead Sponsor
- Grand Hôpital de Charleroi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 57
1.Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
2.Female aged > 18 years at time of study entry.
3.Patient has T1, N1 or T2-T3 any N, M0, operable breast cancer
4.Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma
5.TNBC defined as negative oestrogen and progesterone receptors as per local laboratory testing and negative HER2 defined as negative ISH test or and IHC status of 0 or 1+ as per local laboratory testing
6.Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone receptors, a negative HER2 defined as negative ISH test or and IHC status of 0 or 1+ as per local laboratory testing and a Ki67 > 14%.
7.World Health Organisation (WHO) performance status of 0 or 1
8.Adequate normal organ and marrow function as defined below:
a.Haemoglobin = 9.0 g/dL
b.Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3)
c.Platelet count = 100 x 109/L (>100,000 per mm3)
d.Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert’s syndrome (persistent or
recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology).
AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit
Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
creatinine CL (mL/min)=(Weight (kg) ×(140 – Age))/( 72 × serum creatinine (mg/dL))×0.85
9.Subjects must either be postmenopausal or must have a negative serum pregnancy test upon study entry. Women will be considered postmenopausal if they are:
a.post-menopausal by history: = 60 years old and no menses for ?1 year without an alternative medical cause
b.OR history of hysterectomy
c.OR history of bilateral tubal ligation
d.OR history of bilateral oophorectomy
10.Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2.Previous enrolment in the present study
3.Participation in another clinical study with an investigational product during the last 4 weeks
4.Patient has locally recurrent or metastatic BC
5.Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease
6.History of another primary malignancy except for:
a.Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence
b.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c.Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
7.Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) = 21 days prior to the first dose of study drug
8.Any previous treatment with a PD1 or PD-L1 inhibitor, including Durvalumab
9.Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
10.Current or prior use of immunosuppressive medication within 28 days before the first dose of Durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
11.Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia’s Correction
12.Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
13.Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
14.History of primary immunodeficiency
15.History of allogeneic organ transplant
16.History of hypersensitivity to Durvalumab or any excipient
17.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
18.Subjects with uncontrolled seizures.
19.Known history of active tuberculosis
20.Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving Durvalumab
21.Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control
22.Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of Durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer (BC)<br>;Secondary Objective: To explore efficacy of Durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer. <br>To prolong evaluation of the phase Ib concerning the safety and tolerability of Durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early BC;Primary end point(s): AEs based on physical examinations, vital signs including blood pressure, pulse, electrocardiograms, and laboratory findings including clinical chemistry, haematology and urinalysis. <br>pCR on resected tumor ;Timepoint(s) of evaluation of this end point: January 2018
- Secondary Outcome Measures
Name Time Method Secondary end point(s): ORR based on breast MRI assessment pre and post neoadjuvant treatment <br>AEs based on physical examinations, vital signs including blood pressure, pulse, electrocardiograms, and laboratory findings including clinical chemistry, haematology and urinalysis;Timepoint(s) of evaluation of this end point: January 2018