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

Primary Purpose

Luminal B

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Durvalumab
Stereotactic Body Radiotherapy
Oleclumab
Sponsored by
Jules Bordet Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Luminal B focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years old
  • Female
  • ECOG performance status ≤ 1
  • Weight ≥ 35 kg
  • Histological diagnosis of invasive breast adenocarcinoma that is estrogen receptorpositive, and HER2- negative as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing -ER-positive is defined as having an immunohistochemistry (IHC) of 1% or more and/or and Allred score of 3 or more

    • HER2 negative is defined as having an IHC of 0 or 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number < 4 signals/cells [without IHC]; note: a IHC of 3+ is always considered HER2 positive, independently of the ISH result.
  • Agreement to perform new study related biopsies to provide tissue samples
  • Confirmed Mammaprint genomic high risk score according to centralised testing. Mammaprint will only be tested for luminal B breast tumours with either Proliferation Index Ki67 ≥ 15% or histology grade 3 tumours. (Testing to be done during screening period).In case the MammaPrint test returns an unevaluable result or is technically impossible, the sponsor should be contacted as soon as possible to discuss the inclusion of the concerned patient. Under some specific medical conditions and breast cancer disease characteristics, the medical team of the sponsor can accept that the site continues the screening process of the patient. There will be maximum 5% of nonevaluable Mammaprint results among enrolled patients.
  • Tumour size:

    - If subject is cN0: tumour size ≥ 2 cm, as determined by MRI imaging.

    • If subject is cN1, cN2 or cN3: tumour size ≥ 1.5 cm, as determined by MRI imaging.
  • Multifocal, multicentric unilateral or bilateral breast adenocarcinoma tumours are allowed provided that all foci are ER+/HER2- according to local testing and all foci are able to receive SBRT treatment within the defined dosimetric constraints. For bilateral, multifocal or multicentric disease, the site selected for pre-treatment biopsy should correspond to the site of largest measurable disease meeting eligibility criteria. The location of tumour biopsy site (laterality, quadrant, position from the nipple and type of imaging modality to guide biopsy) should be collected.
  • Serum pregnancy test (for subjects of childbearing potential) negative within 2 weeks prior to first dose of study administration.
  • Women of childbearing potential must agree to use 1 highly effective method of contraception during the screening period, during the course of the study and at least 12 months after the last administration of study treatment. it is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period.
  • Adequate bone marrow function as defined below:

    - Absolute neutrophil count ≥1500/µL, i.e. 1.5x10^9/L

    - Hemoglobin ≥ 9.0 g/dL

    - Platelets ≥100000/µL, i.e. 100x10^9/L

  • Adequate liver function as defined below:

    • Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome ≤ 3 x UNL is allowed
    • AST (SGOT) ≤ 3.0 x ULN
    • ALT (SGPT) ≤ 3.0 x ULN
  • Adequate renal function as defined below:

    • Creatinine ≤ 1.5 x UNL or eGFR ≥ 40ml/min/1.73m²
  • Adequate coagulant function as defined below:

    • International Normalized Ratio (INR) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as INR and activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
  • Completion of all necessary screening procedures within 21 days prior to randomisation.
  • Willingness to provide tissue and blood samples for immuno-monitoring and translational research activities
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF performed in routine is accepted if done within 6 months prior to beginning of screening.
  • Signed Informed Consent form (ICF) obtained prior to any study related procedure.

Inclusion criterion for phase II only (all phase II subjects):

• Tumour sample provided for central PD-L1 IHC assessment. (Testing done during screening period).

Inclusion criterion applicable to FRANCE only (all safety run-in and phase II subject):

• Affiliated to the French Social Security System (applicable only to subjects treated in France)

Exclusion Criteria:

  • Pregnant and/or lactating women.
  • Subject with a significant medical, neuro-psychiatric, substance abuse or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
  • TNM stage cT4 breast cancer including inflammatory breast cancer
  • Presence of any distant metastasis
  • Contra-indication for treatment by paclitaxel, doxorubicin or cyclophosphamide, or known allergy to any tested substances or any excipients (e.g; chemotherapy or immunotherapy formulations). Contra-indication for subjects with known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine (this is a contra-indication for treatment with oleclumab).
  • Previously known contra-indication for treatment by radiation therapy such as rare genetic disorders associated with DNA repair disorders such as ataxia-telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Fanconi anemia.
  • Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis) within the past 3 years. NOTE: Subjects with childhood atopy or asthma, vitiligo, alopecia, Grave's disease, Hashimoto's thyroiditis, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • Prior malignancy active within the previous 5 years, except for localised cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence. Examples include basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast
  • Known history of, or any evidence of active, non-infectious pneumonitis.
  • Active infection including:

    • Tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
    • Hepatitis B (known positive HBV surface antigen (HBsAg) result). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
    • Hepatitis C. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, transient ischemic attack, or stroke within the previous 3 months, unstable arrhythmias, and/or unstable angina
  • Medical condition requiring current systemic anticoagulation, or a history of congenital hypercoagulable condition. Subjects taking aspirin at doses < 325 mg per day are eligible provided that prothrombin time is within the institutional range of normal. Use of local anticoagulation for port maintenance is permitted.
  • Subjects with history of venous thrombosis in the past 12 months prior to the scheduled first dose of study treatment (oleclumab).
  • Diabetes mellitus Type 1 or poorly controlled Type 2 diabetes mellitus defined as a screening hemoglobin A1C ≥ 8 % or a fasting plasma glucose ≥ 160 mg/dL (or 8.8 mmol/L)
  • Any live (attenuated) vaccine within 30 days of planned start of study therapy.
  • Prior systemic immunosuppressive medication (excluding corticosteroids) within 30 days of planned start of study therapy.
  • Prior radiation therapy to the ipsilateral breast.
  • Prior immunotherapy, including tumour vaccine, cytokine, anti-CTLA4, PD-1/PD-L1, including durvalumab, blockage or similar agents.
  • Concomitant use of other investigational drugs
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Subjets with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or oleclumab may be included only after consultation with the Study Physician.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Prior organ transplantation
  • Subjects with urinary outflow obstruction

Exclusion criterion applicable to FRANCE only

• Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.

Sites / Locations

  • Institut Jules BordetRecruiting
  • Cliniques Universitaires Saint-Luc
  • Universitaire ZiekenhuizenRecruiting
  • CHU UCL Namur Sainte-ElisabethRecruiting
  • GZA - Ziekenhuizen (Campus St. Augustinus)Recruiting
  • Centre Georges François LeclercRecruiting
  • Institut CurieRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Chemotherapy and radiotherapy

Chemotherapy and pre-operative radiotherapy plus durvalumab

Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab

Arm Description

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).

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) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w.

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) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w and the addition of the anti-CD73 antibody oleclumab IV 3000 mg q2w for 4 administrations, followed by q4w for 3 administrations.

Outcomes

Primary Outcome Measures

Safety Run-in: Evaluation of the immune related or radiation therapy related toxicity of special interest
Immune related or radiation therapy related toxicity of special interest are identifitied as: Any Grade 4 immune-related AE Any ≥ Grade 3 colitis Any ≥ Grade 3 renal failure/nephritis Any ≥ Grade 3 non-infectious pneumonitis irrespective of duration Any Grade 3 immune-related AE, excluding colitis, renal failure/nephritis and pneumonitis, that does not downgrade to ≤ Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or does not downgrade to ≤ Grade 1 or baseline within 14 days Liver transaminase elevation ≥ 5 ULN or total bilirubin > 3 × ULN will be considered a DLT regardless of duration or reversibility Any increase in AST or ALT > 3 × ULN and concurrent increase in total bilirubin > 2 × ULN
Safety Run-in: Evaluation of the feasibility of the primary surgery
Feasibility of performing surgery within 6 weeks after the last neo-adjuvant treatment. This would indicate that there were no significant delays or toxicities that would results in surgery being delayed.
Phase II: Demonstration of the tumour response in arms 2 or 3 versus arm 1
To demonstrate improved tumour response of the primary tumour and nodal metastases in arms 2 or 3 versus arm 1 using residual cancer burden (RCB 0-1 vs. RCB 2-3) at time of surgery.

Secondary Outcome Measures

Phase II: Evaluation of the response to the primary tumour irrespective of the response to the pathological lymph nodes
Complete pathologic response rate (pCR) of the primary tumour (ypT0), irrespective of the response rate of the resected nodal metastases
Phase II: Evaluation of the response to the pathological lymph nodes irrespective of the response to the primary tumour
Complete pathological response rate (pCR) of the resected nodal metastases (ypN0), irrespective of the response rate of the primary tumour.
Phase II: Evaluation of the feasibility to perform breast-sparing surgery of the arms 2 and 3 versus arm 1
Calculation of the percentage of breast conservation surgery in arms 2 and 3 versus arm 1
Phase II: Evaluation of the ability to control invasive disease in arms 2 and 3 versus arm 1
Invasive Disease-Free Survival (iDFS) 3 years after surgery.
Phase II: Evaluation of the severity and duration of AEs
Duration and severity of AEs based on CTCAE 5.0.
Phase II: Evaluation of the cosmetic changes to the breast
Evaluation of the breast cosmetic changes using the independently validated Breast Cancer Conservative Treatment Cosmetic Results (BCCT.core) software (Cardoso et al., The Breast, 2007). Digitalized color photographs will be taken at multiple timepoints and the cosmetic changes will be scored quantitatively by the BCCT.core software program. The software performs an automatic calculation and attributes an overall cosmetic score: excellent, good, fair or poor (score 1-4; higher score means worse outcome).

Full Information

First Posted
February 8, 2019
Last Updated
July 7, 2023
Sponsor
Jules Bordet Institute
Collaborators
Institut Curie, AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT03875573
Brief Title
Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer:
Acronym
Neo-CheckRay
Official Title
Neo-adjuvant Chemotherapy Combined With Stereotactic Body Radiotherapy to the Primary Tumour +/- Durvalumab, +/- Oleclumab in Luminal B Breast Cancer: a Phase ll Randomised Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 6, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
January 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute
Collaborators
Institut Curie, AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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: the combination of weekly paclitaxel followed by dose-dense doxorubicin-cyclophosphamide (ddAC) and pre-operative radiation therapy (boost dose) on the primary tumour arm 1 with the addition of the anti-PD-L1 antibody durvalumab 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: 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). Arm 2: drugs regimen of Arm 1 with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w. 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 36 months (every 3 months during the first 24 months and every 6 months during the last 12 months).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Luminal B
Keywords
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
147 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy and radiotherapy
Arm Type
Experimental
Arm Description
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).
Arm Title
Chemotherapy and pre-operative radiotherapy plus durvalumab
Arm Type
Experimental
Arm Description
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) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w.
Arm Title
Chemotherapy & pre-op radiotherapy + durvalumab + oleclumab
Arm Type
Experimental
Arm Description
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) with the addition of the anti-PD-L1 antibody durvalumab IV 1500 mg q4w and the addition of the anti-CD73 antibody oleclumab IV 3000 mg q2w for 4 administrations, followed by q4w for 3 administrations.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
an anti PD-L1 intravenous administration at 1500 mg every 4 weeks for 19 weeks.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiotherapy
Other Intervention Name(s)
SBRT
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Oleclumab
Other Intervention Name(s)
MEDI9447
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety Run-in: Evaluation of the immune related or radiation therapy related toxicity of special interest
Description
Immune related or radiation therapy related toxicity of special interest are identifitied as: Any Grade 4 immune-related AE Any ≥ Grade 3 colitis Any ≥ Grade 3 renal failure/nephritis Any ≥ Grade 3 non-infectious pneumonitis irrespective of duration Any Grade 3 immune-related AE, excluding colitis, renal failure/nephritis and pneumonitis, that does not downgrade to ≤ Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or does not downgrade to ≤ Grade 1 or baseline within 14 days Liver transaminase elevation ≥ 5 ULN or total bilirubin > 3 × ULN will be considered a DLT regardless of duration or reversibility Any increase in AST or ALT > 3 × ULN and concurrent increase in total bilirubin > 2 × ULN
Time Frame
7 months
Title
Safety Run-in: Evaluation of the feasibility of the primary surgery
Description
Feasibility of performing surgery within 6 weeks after the last neo-adjuvant treatment. This would indicate that there were no significant delays or toxicities that would results in surgery being delayed.
Time Frame
7 months
Title
Phase II: Demonstration of the tumour response in arms 2 or 3 versus arm 1
Description
To demonstrate improved tumour response of the primary tumour and nodal metastases in arms 2 or 3 versus arm 1 using residual cancer burden (RCB 0-1 vs. RCB 2-3) at time of surgery.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Phase II: Evaluation of the response to the primary tumour irrespective of the response to the pathological lymph nodes
Description
Complete pathologic response rate (pCR) of the primary tumour (ypT0), irrespective of the response rate of the resected nodal metastases
Time Frame
24 months
Title
Phase II: Evaluation of the response to the pathological lymph nodes irrespective of the response to the primary tumour
Description
Complete pathological response rate (pCR) of the resected nodal metastases (ypN0), irrespective of the response rate of the primary tumour.
Time Frame
24 months
Title
Phase II: Evaluation of the feasibility to perform breast-sparing surgery of the arms 2 and 3 versus arm 1
Description
Calculation of the percentage of breast conservation surgery in arms 2 and 3 versus arm 1
Time Frame
24 months
Title
Phase II: Evaluation of the ability to control invasive disease in arms 2 and 3 versus arm 1
Description
Invasive Disease-Free Survival (iDFS) 3 years after surgery.
Time Frame
24 months
Title
Phase II: Evaluation of the severity and duration of AEs
Description
Duration and severity of AEs based on CTCAE 5.0.
Time Frame
24 months
Title
Phase II: Evaluation of the cosmetic changes to the breast
Description
Evaluation of the breast cosmetic changes using the independently validated Breast Cancer Conservative Treatment Cosmetic Results (BCCT.core) software (Cardoso et al., The Breast, 2007). Digitalized color photographs will be taken at multiple timepoints and the cosmetic changes will be scored quantitatively by the BCCT.core software program. The software performs an automatic calculation and attributes an overall cosmetic score: excellent, good, fair or poor (score 1-4; higher score means worse outcome).
Time Frame
24 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Must be female by biological birth.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years old Female ECOG performance status ≤ 1 Weight ≥ 35 kg Histological diagnosis of invasive breast adenocarcinoma that is estrogen receptor-positive (ER-positive) and HER2- negative, as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines and performed according to local testing. In addition, only tumours with Proliferation Index Ki67 ≥ 15% or histology grade III are accepted. Agreement to perform new study related biopsies to provide tissue samples MammaPrint genomic high risk score according to centralised testing, except for specific conditions as mentioned below. Mammaprint will only be tested for luminal B breast tumours with either Proliferation Index Ki67 ≥ 15% or histology grade III tumours. (Testing to be done during screening period). MammaPrint result status at time of termination of all other screening procedures MammaPrint is high risk: subject may be randomized. MammaPrint is low risk: subjet can not be randomized. MammaPrint result is not yet known: If the MammaPrint result is not known at time of termination of all other screening procedures, the investigator is allowed to randomize the subject and start study treatment without waiting for the result of the MammaPrint in the following situations: (Ki67 > 20 % or grade III) and Age<50 years+ cN0 OR Age ≥ 50 years + cN+ • Tumour size: If subject is cN0: tumour size ≥ 2 cm, as determined by MRI imaging. If subject is cN1, cN2 or cN3: tumour size ≥ 1.5 cm, as determined by MRI imaging. The requirement for an MRI is not applicable in the case of medical contraindications to perform MRI (e.g., obesity or claustrophobia). In this situation, tumour evaluations should be performed by ultrasound. Multifocal, multicentric unilateral or bilateral breast adenocarcinoma tumours are allowed provided that all biopsiable foci are ER+/HER2- according to local testing and all foci are able to receive SBRT treatment within the defined dosimetric constraints. In some cases a separate biopsy of every focus is not mandatory, but only if every of the following conditions are present: -small focal lesion -lesion in close proximity to the main primary cancer from which a biopsy was taken the investigator and the radiologist consider the lesion to be clearly related to the main primary breast cancer from which a biopsy was taken the lesion will be removed during the same lumpectomy than the main primary breast cancer For bilateral, multifocal or multicentric disease, the site selected for pre-treatment biopsy should correspond to the site of largest measurable disease meeting eligibility criteria. The location of tumour biopsy site (laterality, quadrant, position from the nipple and type of imaging modality to guide biopsy) should be collected. Serum pregnancy test (for subjects of childbearing potential) negative within 2 weeks prior to first dose of study administration. Women of childbearing potential must agree to use 1 highly effective method of contraception during the screening period, during the course of the study and at least 12 months after the last administration of study treatment. it is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Adequate bone marrow function as defined below: Absolute neutrophil count ≥1500/µL, i.e. 1.5x10^9/L Hemoglobin ≥ 9.0 g/dL Platelets ≥100000/µL, i.e. 100x10^9/L Adequate liver function as defined below: - Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome ≤ 3 x UNL is allowed - AST (SGOT) ≤ 3.0 x ULN ALT (SGPT) ≤ 3.0 x ULN Adequate renal function as defined below: Creatinine ≤ 1.5 x UNL or eGFR ≥ 40ml/min/1.73m² Adequate coagulant function as defined below: International Normalized Ratio (INR) ≤ 1.5 x ULN Completion of all necessary screening procedures within 28 days prior to randomisation (except if written differently). Willingness to provide tissue and blood samples for immuno-monitoring and translational research activities Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF performed in routine is accepted if done within 6 months prior to beginning of screening. Signed Informed Consent form (ICF) obtained prior to any study related procedure. Inclusion criterion for phase II only (all phase II subjects): • Tumour sample provided for central PD-L1 IHC assessment. (Testing done during screening period). Inclusion criterion applicable to FRANCE only (all safety run-in and phase II subject): • Affiliated to the French Social Security System (applicable only to subjects treated in France) Exclusion Criteria: Pregnant and/or lactating women. Subject with a significant medical, neuro-psychiatric, substance abuse or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study. TNM stage cT4 breast cancer including inflammatory breast cancer Presence of any distant metastasis Contra-indication for treatment by paclitaxel, doxorubicin or cyclophosphamide, or known allergy to any tested substances or any excipients (e.g; chemotherapy or immunotherapy formulations). Contra-indication for subjects with known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine (this is a contra-indication for treatment with oleclumab). Previously known contra-indication for treatment by radiation therapy such as rare genetic disorders associated with DNA repair disorders such as ataxia-telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Fanconi anemia. Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis) within the past 3 years. NOTE: Subjects with childhood atopy or asthma, vitiligo, alopecia, Grave's disease, Hashimoto's thyroiditis, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded Prior malignancy active within the previous 5 years, except for localised cancers that are considered to have been cured and in the opinion of the investigator present a low risk for recurrence. Examples include basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast Known history of, or any evidence of active, non-infectious pneumonitis. Active infection including: Tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice) Hepatitis B (known positive HBV surface antigen (HBsAg) result). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Hepatitis C. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, transient ischemic attack, or stroke within the previous 3 months, unstable arrhythmias, and/or unstable angina Medical condition requiring current systemic anticoagulation, or a history of congenital hypercoagulable condition. Subjects taking aspirin at doses < 325 mg per day are eligible provided that prothrombin time is within the institutional range of normal. Use of local anticoagulation for port maintenance is permitted. Subjects with history of venous thrombosis in the past 12 months prior to the scheduled first dose of study treatment (oleclumab). Diabetes mellitus Type 1 or poorly controlled Type 2 diabetes mellitus defined as a screening hemoglobin A1C ≥ 8 % or a fasting plasma glucose ≥ 160 mg/dL (or 8.8 mmol/L) Any live (attenuated) vaccine within 30 days of planned start of study therapy. Prior systemic immunosuppressive medication (excluding corticosteroids) within 30 days of planned start of study therapy. Prior radiation therapy to the ipsilateral breast. Prior immunotherapy, including tumour vaccine, cytokine, anti-CTLA4, PD-1/PD-L1, including durvalumab, blockage or similar agents. Concomitant use of other investigational drugs Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Subjets with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or oleclumab may be included only after consultation with the Study Physician. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Prior organ transplantation Subjects with urinary outflow obstruction Exclusion criterion applicable to FRANCE only • Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alex De Caluwe, MD
Phone
+3225413485
Email
alex.decaluwe@bordet.be
First Name & Middle Initial & Last Name or Official Title & Degree
Diane Delaroche
Email
ctsu.neocheckray@bordet.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alex De Caluwe, MD
Organizational Affiliation
Jules Bordet Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Jules Bordet
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurence Buisseret, MD
Phone
+32 2 541 38 43
Email
laurence.buisseret@bordet.be
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eleonore Longton, MD
Facility Name
Universitaire Ziekenhuizen
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adinda Baten, MD
Phone
+32471573165
Email
adinda.baten@uzleuven.be
Facility Name
CHU UCL Namur Sainte-Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Remouchamps, MD
Phone
+3281720525
Email
vincent.remouchamps@uclouvain.be
Facility Name
GZA - Ziekenhuizen (Campus St. Augustinus)
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philip Poortmans, MD
Phone
+32496892263
Email
philip.poortmans@gza.be
Facility Name
Centre Georges François Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabelle Desmoulins, MD
Phone
+33 3 80 73 75 28
Email
idesmoulins@cgfl.fr
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75248
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emanuela Romano, MD
Phone
+33 172 3893 35
Email
emanuela.romano@curie.fr

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34362344
Citation
De Caluwe A, Buisseret L, Poortmans P, Van Gestel D, Salgado R, Sotiriou C, Larsimont D, Paesmans M, Craciun L, Stylianos D, Vandekerckhove C, Reyal F, Isabelle V, Eiger D, Piccart M, Romano E, Ignatiadis M. Neo-CheckRay: radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer, a randomized phase II trial. BMC Cancer. 2021 Aug 6;21(1):899. doi: 10.1186/s12885-021-08601-1.
Results Reference
derived

Learn more about this trial

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

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