Clinical Trials /

Safety and Efficacy of Durvalumab Combined to Neoadjuvant Chemotherapy in Localized Luminal B HER2(-) and Triple Negative Breast Cancer.

NCT03356860

Description:

The study has a phase Ib and a phase II part. - The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer. - The phase II aims to explore the efficacy of durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer.

Related Conditions:
  • Breast Invasive Ductal Carcinoma
  • Breast Invasive Lobular Carcinoma
  • Medullary Breast Carcinoma
  • Mixed Lobular and Ductal Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of Durvalumab Combined to Neoadjuvant Chemotherapy in Localized Luminal B HER2(-) and Triple Negative Breast Cancer.
  • Official Title: 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.

Clinical Trial IDs

  • ORG STUDY ID: ONCOGHdC2015_01
  • NCT ID: NCT03356860

Conditions

  • Breast Cancer
  • Triple Negative Breast Cancer
  • Luminal B

Interventions

DrugSynonymsArms
PaclitaxelTaxolDurvalumab
EpirubicinFarmorubicineDurvalumab
CyclophosphamideEndoxanDurvalumab
DurvalumabMEDI4736Durvalumab

Purpose

The study has a phase Ib and a phase II part. - The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer. - The phase II aims to explore the efficacy of durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer.

Trial Arms

NameTypeDescriptionInterventions
DurvalumabExperimentalPatients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20. Durvalumab will be administered at 1500 mg IV at week 14 and week 18.
  • Paclitaxel
  • Epirubicin
  • Cyclophosphamide
  • Durvalumab
StandardActive ComparatorPatients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20.
  • Paclitaxel
  • Epirubicin
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and any locally-required authorization (EU Data Privacy
             Directive in the EU) obtained from the subject prior to performing any
             protocol-related procedures, including screening evaluations

          -  Female and male aged > 18 years at time of study entry.

          -  Patient has T1-T4 any N, M0, operable breast cancer

          -  Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma

          -  TNBC defined as negative oestrogen and progesterone receptors as per local laboratory
             testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as
             per local laboratory testing

          -  Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone
             receptors, a negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as
             per local laboratory testing and a Ki67 > 14%.

          -  World Health Organisation (WHO) performance status of 0 or 1

          -  Adequate normal organ and marrow function as defined below:

               1. Haemoglobin ≥ 9.0 g/dL

               2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)

               3. Platelet count ≥ 100 x 109/L (>100,000 per mm3)

               4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).

               5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit

               6. Serum creatinine CL>40 mL/min

          -  Normal cardiac function must be confirmed by ECG and cardiac function assessed by US
             imagery, radionucleotide ventriculography or MUGA, 4 weeks prior to randomization.
             Results must be above the normal limit of the institution

          -  Women must either be postmenopausal or must have a negative serum pregnancy test 14
             days upon study entry.

          -  For a woman of childbearing potential, an effective method of birth control must be
             employed.

          -  Men must use 2 effective contraceptive measures or male sterilization with female
             partners of childbearing potential or pregnant female partners, or they must remain
             abstinent during the treatment period and for at least 6 months after the last dose of
             the study treatment.

          -  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.

          -  Subject accepts planned biological samples collection and their use for the trial
             propose.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study

          -  Previous enrolment in the present study

          -  Participation in another clinical study with an investigational product during the
             last 4 weeks

          -  Patient has locally recurrent or metastatic invasive BC

          -  History of another primary malignancy except for:

               1. Malignancy treated with curative intent and with no known active disease ≥5 years
                  before the first dose of study drug

               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               3. Adequately treated carcinoma in situ without evidence of disease eg, cervical
                  cancer in situ or BC in situ.

          -  Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy,
             immunotherapy) or radiotherapy for current breast cancer disease

          -  Whatever the indication, receipt of a 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

          -  Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab

          -  Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved irAE >Grade 1

          -  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

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from
             electrocardiograms (ECGs) using Fridericia's Correction

          -  Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease,
             angina pectoris requiring antianginal medication, previous history of myocardial
             infarction, evidence of transmural infarction on ECG, uncontrolled or poorly
             controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two
             antihypertensive drugs), rhythm abnormalities requiring permanent treatment,
             clinically significant valvular heart disease.

          -  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.

          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

          -  History of primary immunodeficiency

          -  History of allogeneic organ transplant

          -  History of hypersensitivity to durvalumab or any excipient

          -  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

          -  Subjects with uncontrolled seizures.

          -  Known history of active tuberculosis

          -  Anticipation that a live attenuated vaccine will be required during the period from 30
             days prior to the first planned durvalumab administration (e.i. week 18 and week 14
             after study entry for the phase Ib and phase II respectively) to 5 months of
             durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live
             attenuated forms) should be given during influenza season only (approximately October
             to March).

          -  Female subjects who are pregnant, breast-feeding or female patients of reproductive
             potential who are not employing an effective method of birth control

          -  Men with female partners of childbearing potential or pregnant female partners who are
             not employing an effective method of birth control

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:74 weeks
Safety Issue:
Description:(serious) adverse event will be recorded

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Grand Hôpital de Charleroi

Trial Keywords

  • breast cancer
  • immunotherapy
  • anti-PD-L1

Last Updated

May 28, 2020