A phase II study investigating preoperative combination strategies for immunotherapy in patients with untreated, operable oestrogen receptor positive primary breast cancer
- Conditions
- ntreated, operable ER+, HER2-negative primary breast cancer.MedDRA version: 21.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004424-38-GB
- Lead Sponsor
- Queen Mary University of London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 57
1. Willing and able to provide written informed consent prior to study entry
2. Female = 18 years of age
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
4. Histologically confirmed operable primary breast cancer
5. Palpable breast tumour of any size, or tumour with an ultrasound / MRI size of = 1 cm or mammogram
6. ER+ tumours defined as tumours with =1% of tumour cells positive for ER on IHC staining or an IHC score (Allred) of = 3
7. HER2-negative tumours defined as 0, 1+ or 2+ intensity on IHC and no evidence of amplification of the HER2 gene on ISH.
8. Patients with either: (a) Luminal B breast cancer defined as: high Ki67 defined as =20% and /or histological grade 3 and / or Luminal B according to PAM50 assay OR (b) Non-Luminal B breast cancer
9. Adequate haematologic and end-organ function within 28 days prior to the first study treatment.
10. Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test within 14 days of Day 1 Cycle 1 of study treatment, preferably as close to the first dose as possible. Patients must agree to use adequate contraception, defined as those methods with a failure rate of < 1 % per year, beginning 14 days before the first dose of study drug and for 6 months after the last dose of study drug.
11. Ability to comply with the protocol
12. Representative formalin-fixed paraffin embedded (FFPE) breast tumour samples with an associated pathology report that are determined to be available and sufficient for central testing OR tumour accessible for biopsy.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
1. Inflammatory breast cancer
2. Concurrent use of HRT.
3. Previous systemic or local treatment for the new primary breast cancer currently under investigation; prior treatment for previous breast cancer or other neoplasms is allowed as long as it was completed =1 year prior to Day 1 Cycle 1.
4. Previous systemic treatment for other neoplasms within 1 year prior to randomisation.
5.Patients with prior allogeneic stem cell or solid organ transplantation.
6. Prior treatment with CD137 agonists, AKT inhibitors, anti-CTLA-4, anti- PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
7.Patients must not have had oral or IV steroids for 14 days prior to study entry; the use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids and mineralocorticoids is allowed.
8. Received therapeutic oral or intravenous antibiotics <14 days prior to randomisation.
9. Administration of a live, attenuated vaccine <28 days prior to randomisation, treatment, or within 5 months following the last dose of atezolizumab.
10. Treatment with systemic immunostimulatory agents <28days or five half-lives of the drug, whichever is shorter, prior to enrolment.
11. History of autoimmune disease. Patients with autoimmune-related hypothyroidism on a stable dose of thyroid replacement therapy may be eligible for the study following discussion with the medical monitor.
12. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan.
13. History of HIV infection
14. Known active hepatitis infection or hepatitis C.
15. Active tuberculosis
16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
17. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
19. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
20. Concurrent treatment with other experimental drugs or participation in another clinical trial with therapeutic intent < 28 days prior to randomisation.
21. Pregnant and lactating female patients.
22. Major surgical procedure < 4 weeks prior to randomisation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
23. Malignancies other than breast cancer < 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
24. Severe infections < 28 days prior to enrolment in the study including b
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): 2-fold increase in GzmB+ CD8+ T cell levels from baseline to end of treatment sample. ;Timepoint(s) of evaluation of this end point: Samples collected pre-treatment and on completion of treatment. ;Main Objective: To determine whether adding immune-modulatory agents to atezolizumab increases the probability of an immune response over atezolizumab alone in patients with operable ER+ breast cancer. ;<br> Secondary Objective: • Status and changes of the biomarkers listed below in pre- and end-of treatment tumour and/or blood samples: Immunephenotyping, CD8, PD-L1, MHC-I,immune infiltrates (IFNg gene signature expression).<br><br> • Percentage change in Ki67 expression and caspase-3 expression between pre- and end of study-treatment tumour biopsies.<br><br> • Incidence, nature and severity of adverse events with severity determined according to CTCAE v4.03.<br><br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1. Status and changes of the biomarkers listed below in pre- and end-of treatment tumour and/or blood samples: Immunephenotyping, CD8, PD-L1, MHC-I, immune infiltrates (IFNg gene signature expression).<br><br> 2. Percentage change in Ki67 expression and caspase-3 expression between pre- and end of study-treatment tumour biopsies.<br><br> 3. Incidence, nature and severity of adverse events with severity determined according to CTCAE v4.03.<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Samples collected pre-treatment and on completion of treatment.<br><br> 2. Samples collected pre-treatment and on completion of treatment.<br><br> 3. Consent to 30 days after after the last dose of Atezolizumab.<br>