NCT03875573

Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer:

Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: a Phase ll Randomised Trial

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 147 (actual)
• Sponsor: Jules Bordet Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Neo-CheckRay is a multicenter, open-label phase II study that randomizes luminal B breast cancer subjects candidate for neo-adjuvant chemotherapy in a 1:1:1 ratio in 3 arms: 1. the combination of weekly paclitaxel followed by dose-dense doxorubicin-cyclophosphamide (ddAC) and pre-operative radiation therapy (boost dose) on the primary tumour 2. arm 1 with the addition of the anti-PD-L1 antibody durvalumab 3. arm 2 with the addition of the anti-CD73 antibody oleclumab The primary tumour will be excised 2-6 weeks after completion of ddAC. A safety run-in is planned for the 6 first subjects before starting the randomized phase II trial. Those 6 subjects will receive the treatment given in Arm 3.

Detailed description

This trial consists of a safety run-in followed by a phase II randomised trial. The goal of the safety run-in is to assess the safety of adding SBRT to the neo-adjuvant systemic treatment. The doses of the IMPs will be identical in the safety run-in and the phase II randomised trial. Individual subject timelines are also identical in the safety run-in and the phase II randomised trial. The safety run-in is done as a precursor to the phase II randomised part of the Neo-CheckRay trial. Six subjects will be included in the safety run-in. These subjects are not part of the phase II total recruitment. Subjects in the safety run-in will receive the following treatments corresponding to arm 3 of the phase II randomised trial. This consists of: * q1w paclitaxel 80 mg/m² IV for 12 administration (12 weeks) followed by q2w dose-dense doxorubicin-cyclophosphamide IV (60 mg/m² and 600 mg/m² respectively) for 4 administrations (8 weeks) * Anti-PD-L1 antibody durvalumab 1500 mg IV q4w for 5 administration (20 weeks) * Anti-CD73 antibody oleclumab 3000 mg IV q2w for 4 administrations (8 weeks), followed by q4w for 3 administrations (12 weeks) * Pre-operative radiation therapy (boost dose) 3x8 Gy on the primary tumour at week 5 If all requirements are meet during the safety run-in, then the phase II part of the study will be opened. The phase II will consist of luminal B breast cancer subjects candidate for neo-adjuvant chemotherapy will be randomised in a 1:1:1 ratio between 3 arms: 1. Arm 1: the combination of weekly paclitaxel 80 mg/m² IV followed by q2w dose- dense doxorubicin-cyclophosphamide (ddAC) (60 mg/m² doxorubicin IV and 600 mg/m² cyclophosphamide IV) and pre-operative radiation therapy on the primary tumour (3x8 Gy). 2. Arm 2: drugs regimen of Arm 1 with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w. 3. Arm 3: drugs regimen of Arm 2 with the addition of the anti-CD73 antibody oleclumab IV 3000 mg q2w for 4 administrations, followed by q4w for 3 administrations. The primary tumour will be excised 2-6 weeks after completion of ddAC. The study treatments end at surgery. All treatment after surgery, such as post-operative radiotherapy and hormonal therapy, will be performed according to standard of care and local site guidelines. The patient will then be followed for the next 5 years.

Conditions

• Luminal B

Interventions

Type	Name	Description
DRUG	Durvalumab	an anti PD-L1 intravenous administration at 1500 mg every 4 weeks for 19 weeks.
RADIATION	Stereotactic Body Radiotherapy	Pre-operative radiation therapy (boost dose) 3x8 Gy on the primary tumour at week 5 given in 3 fractions. The 3 fractions will be spread at the minimum over 3 days and at the maximum over 6 days.
DRUG	Oleclumab	an anti-CD73 intravenous administration at 3000 mg every 2 weeks for the first 4 administrations then every 4 weeks for the last 3 administrations.

Timeline

• Start date: 2019-11-06
• Primary completion: 2025-05-30
• Completion: 2029-09-30
• First posted: 2019-03-14
• Last updated: 2024-12-20

Locations

7 sites across 2 countries: Belgium, France