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.
Overview
- Phase
- Phase 1
- Intervention
- Cyclophosphamide
- Conditions
- Breast Cancer
- Sponsor
- Grand Hôpital de Charleroi
- Enrollment
- 57
- Locations
- 4
- Primary Endpoint
- Adverse events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
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:
- •Haemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
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:
- •Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •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
Arms & Interventions
Durvalumab
Patients 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.
Intervention: Cyclophosphamide
Durvalumab
Patients 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.
Intervention: Paclitaxel
Durvalumab
Patients 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.
Intervention: Epirubicin
Durvalumab
Patients 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.
Intervention: Durvalumab
Standard
Patients 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.
Intervention: Paclitaxel
Standard
Patients 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.
Intervention: Epirubicin
Standard
Patients 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.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Adverse events
Time Frame: 74 weeks
(serious) adverse event will be recorded
Pathological response
Time Frame: 24 weeks
Rate of complete pathological responses will be evaluated as a surrogate endpoint to evaluate efficacy