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

NCT03356860 | Completed Phase 1

• 1 other identifier: ONCOGHdC2015_01
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer; Triple Negative Breast Cancer; Luminal B

Keywords

breast cancer; immunotherapy; anti-PD-L1

Outcome Measures

Primary Outcomes (2)

• Adverse events

  (serious) adverse event will be recorded

  74 weeks

• Pathological response

  Rate of complete pathological responses will be evaluated as a surrogate endpoint to evaluate efficacy

  24 weeks

Study Arms (2)

Durvalumab

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Durvalumab

Standard

ACTIVE COMPARATOR

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.

Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

Paclitaxel DRUG

80mg/m2 IV weekly from week 1 to week12

Also known as: Taxol

Durvalumab; Standard

Epirubicin DRUG

90 mg/m2 IV Q 2 weeks from week 14 to week 20

Also known as: Farmorubicine

Durvalumab; Standard

Cyclophosphamide DRUG

600 mg/m2 IV Q 2 weeks from week 14 to week 20

Also known as: Endoxan

Durvalumab; Standard

Durvalumab DRUG

Durvalumab 1500 mg IV at week 14 and 18

Also known as: MEDI4736

Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Grand Hôpital de Charleroi: lead
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator

Study Sites (4)

Grand Hôpital de Charleroi

Charleroi, Hainaut, 6000, Belgium

Location

CHU UCL Namur - Sainte-Elisabeth

Namur, Wallonia, 5000, Belgium

Location

CHU UCL Namur - Site Godinne

Yvoir, Wallonia, 5530, Belgium

Location

Cliniques universitaires St Luc

Brussels, 1320, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Paclitaxel; Epirubicin; Cyclophosphamide; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Javier Carrasco, MD, PhD

  GHdC

  PRINCIPAL INVESTIGATOR

• Jean-Luc Canon, MD

  GHdC

  PRINCIPAL INVESTIGATOR

• François Duhoux, MD, PhD

  Cliniques universitaires Saint-Luc (UCL)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: November 29, 2017
• Study Start: April 13, 2017
• Primary Completion: November 21, 2022
• Study Completion: December 31, 2023
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)