Trial Title:
Molecular PD-L1 PET/CT Imaging With 89Zr-atezolizumab in Metastatic Triple Negative Breast Cancer
NCT ID:
NCT05742269
Condition:
Metastatic Triple-Negative Breast Carcinoma
Conditions: Official terms:
Triple Negative Breast Neoplasms
Breast Neoplasms
Atezolizumab
Conditions: Keywords:
89Zr-atezolizumab
PD-L1 PET
predictive biomarker
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
89Zr-atezolizumab PET/CT
Description:
All patients undergo a 89Zr-atezolizumab PET/CT. Allocation to chemotherapy +
atezolizumab in case of a PD-L1 positive tumor (on IHC and/or PET)
Arm group label:
PD-L1 negative disease (on PET and IHC)
Arm group label:
PD-L1 positive disease (on PET and/or IHC)
Summary:
The overarching purpose of this study is to improve precision medicine through more
refined therapy selection for breast cancer patients who are candidates for ICI therapy
(monoclonal antibodies targeting the programmed death ligand 1 (PD-L1) or programmed cell
death protein 1 (PD-1)). The reference standard biomarker for ICI therapy selection is
PD-L1 protein expression measured by immunohistochemistry (IHC). Several disadvantages
exist with this method, the most important ones being inter- and intralesional as well as
spatial heterogeneity in PD-L1 expression, as well as the need for invasive procedures to
obtain material for analysis. The study hypothesis is that Positron Emission Tomography
combined with Computed Tomography (PET/CT) imaging with a contemporary radiotracer
(89Zr-atezolizumab), visualizing PD-L1 expression in the whole body, could be a better
predictive biomarker to select which patients benefit from ICI. The use of PET/CT imaging
with new radiotracers enables a non-invasive assessment of the presence of the target of
treatment in the whole body and provides the possibility to combine functional
information with anatomical details.
Detailed description:
Patients with mTNBC scheduled for first line palliative systemic treatment with
nab-paclitaxel and carboplatin can be included. This chemotherapy combination is used to
maximize the therapeutic potential of this first line systemic treatment line,
extrapolating signals from early TNBC and in the absence of signs that indicate augmented
safety issues.
The investigational medical product is 89Zr-atezolizumab. The pharmaceutical preparation
of the IMP consists of the precursor atezolizumab combined with zirconium-89 to form
89Zr-atezolizumab. The radiolabelling of atezolizumab will be performed at the Department
of Radiopharmacy, Karolinska University Hospital, Solna. This involves an automated
synthesis procedure in a Good Manufacturing Practice facility.
All patients are scheduled for treatment with nab-paclitaxel at a dose of 100 mg per
square meter of body-surface area, administered intravenously, on days 1, 8, and 15, and
carboplatin at a dose of Area Under the Curve (AUC) 5 on day 1 of every 28-day cycle. The
patients with a PD-L1+ tumour according to IHC with the SP142 antibody (≥ 1% on immune
cells) and/or 89Zr-atezolizumab tracer uptake on PET-imaging, will receive atezolizumab
at a dose of 840 mg, administered intravenously, on days 1 and 15.
Criteria for eligibility:
Study pop:
Patients with newly diagnosed irresectable or metastatic triple negative breast cancer
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
- Patients with metastatic triple negative breast cancer (mTNBC), defined by
pathological criteria: oestrogen receptor expression <10%, progesterone receptor
expression <10%, HER2 negative, on the primary tumour or a metastatic biopsy
- Measurable disease according to RECIST v1.1
- At least one metastatic lesion accessible for biopsy
- Deemed by treating physician as fit for systemic therapy according to study protocol
- ECOG performance score 0/1
- Age ≥ 18 years old
- Adequate blood tests for bone marrow, renal and hepatic functions
- Able and willing to provide written informed consent
Exclusion Criteria:
- Previous treatment with chemotherapy or targeted therapy for mTNBC. Radiation
therapy and previous chemotherapy (including taxanes) in the context of curative
therapy is allowed.
- Contraindications for PET/CT as defined for clinical practice
- Other malignancy diagnosed within the last five years, except for radically treated
basal or squamous cell carcinoma of the skin or CIS of the cervix
- Patients in child-bearing age without adequate contraception. Examples of
contraceptive methods with a failure rate of < 1% per year include bilateral tubal
ligation, male sterilization, established, proper use of hormonal contraceptives
that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper
IUDs. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of contraception.
Women must refrain from donating eggs during this same period.
- Pregnancy or lactation
- Uncontrolled hypertension, heart-, liver-, or kidney-diseases or other
medical/psychiatric disorders.
- History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis
- Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone are eligible for this study. Patients with
controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible
for this study.
- Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with
dermatologic manifestations only (e.g., no psoriatic arthritis) are permitted
provided that they meet the following conditions: Rash must cover less than 10%
of body surface area (BSA); Disease is well controlled at baseline and only
requiring low potency topical steroids; No acute exacerbations of underlying
condition within the last 12 months (not requiring PUVA [psoralen plus
ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral
calcineurin inhibitors, high potency or oral steroids).
- Vaccination with a live vaccine within 30 days of the first dose of study treatment
- A known history of Human Immunodeficiency Virus (HIV) infection, hepatitis B (HBsAg
reactive) or hepatitis C (HCV RNA detected) infection or active tuberculosis.
- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor [TNF] agents) within 2 weeks prior to randomization, or anticipated
requirement for systemic immunosuppressive medications during the trial
- Patients who have received acute, low-dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
in the study
- Patients with a history of allergic reaction to IV contrast requiring steroid
pre-treatment should have baseline and subsequent tumor assessments performed
using CT.
- The use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
- Hypersensitivity to atezolizumab
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Karolinska University Hospital
Address:
City:
Stockholm
Zip:
171 76
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Agneta Lindeberg, RN
Email:
agneta.lindeberg@regionstockholm.se
Investigator:
Last name:
Renske Altena, MD, PhD
Email:
Principal Investigator
Start date:
July 1, 2023
Completion date:
May 20, 2027
Lead sponsor:
Agency:
Karolinska University Hospital
Agency class:
Other
Source:
Karolinska University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05742269