Actively Recruiting
PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
Led by Institute of Cancer Research, United Kingdom · Updated on 2025-08-11
119
Participants Needed
6
Research Sites
502 weeks
Total Duration
On this page
Sponsors
I
Institute of Cancer Research, United Kingdom
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
PHOENIX is a window of opportunity (WOP), open-label, multi-centre, phase IIa trial comprising multiple non-comparative treatment cohorts with patient allocation via minimisation (cohorts A-D) or allocation according to HRD and germline BRCA1/2 mutation status (cohorts E-G). The trial consists of two parts: a post-neoadjuvant treatment preoperative WOP component (PART 1); and a post-operative component (PART 2). Cohorts A-D: To assess whether short exposure to a DDR inhibitor or anti-PD-L1 immunotherapy in a preoperative WOP in patients with post-NACT high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue. Cohort E: To assess whether short exposure to a DDR inhibitor with or without anti-PD-1 immunotherapy in a preoperative WOP in patients with non-HRD associated TNBC and post-neoadjuvant treatment high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue. Cohorts F \& G: To assess whether short exposure to the DDR inhibitor olaparib with or without anti-PD-1 immunotherapy in a preoperative WOP in patients with HRD associated TNBC and post-neoadjuvant treatment high risk residual disease, generates a signal of anti-tumour biological activity within residual disease tissue.
CONDITIONS
Official Title
PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed informed consent form for trial registration
- Age 18 years or older
- Histologically confirmed invasive triple negative breast cancer (TNBC) defined by specific hormone receptor and HER2 status
- Planned definitive breast surgery after at least 6 cycles of neoadjuvant chemotherapy
- Measurable tumor suitable for marker insertion and repeated biopsies
- Eastern Oncology Cooperative Group (ECOG) performance status 0-1
- Fit for breast cancer surgery with curative intent
- Able to complete at least 2 weeks of pre-operative trial treatment
- Suitable for mandatory pre- and post-treatment biopsies during the window of opportunity
- Staging studies to exclude metastatic disease according to standard care
- Previous invasive cancers allowed if treated over 5 years ago with no recurrence
- No psychological, social, or geographical barriers to trial compliance
- Use of effective contraception or surgical sterilization or post-menopausal status for women of childbearing potential
- Confirmed residual disease of at least 1 cm on trial-specific imaging
- Provision of acceptable archival tumor tissue sample
- Recovery from prior chemotherapy or pembrolizumab side effects to baseline or mild levels
- Adequate blood counts and organ function as defined by trial criteria
- Negative pregnancy test for women of childbearing potential
- Confirmation that all trial registration inclusion criteria remain met
You will not qualify if you...
- Definitive evidence of metastatic disease
- Bilateral breast tumors
- History of another primary cancer within 5 years except certain skin and in situ cancers
- Myelodysplastic syndrome or acute myeloid leukemia or suggestive features
- Severe concurrent disease or infection making trial participation inappropriate
- Uncontrolled cardiac conditions or congenital long QT syndrome
- Inability to swallow oral medication
- Use of therapeutic anti-coagulation treatments
- Gastrointestinal disorders affecting absorption
- History of seizures or conditions predisposing to seizures
- Non-malignant systemic diseases preventing treatment or follow-up
- Pregnancy or breastfeeding
- Prior treatment with PARP inhibitors or anti-PD-1/PD-L1 immunotherapy except pembrolizumab with chemotherapy
- Any disease or condition that contraindicates trial treatment or increases risk
- Known hypersensitivity to pembrolizumab, durvalumab, olaparib, or their components
- Previous allogenic bone marrow or double umbilical cord blood transplant
- Active infections including tuberculosis, hepatitis B or C, or HIV except resolved hepatitis B or negative hepatitis C RNA
- Poor medical risk due to serious uncontrolled disorders or infections
- Major surgery within 2 weeks prior to trial entry
- Use of investigational agents within 30 days prior to treatment
- Concurrent use of certain CYP3A inhibitors or inducers requiring washout
- Whole blood transfusion within 28 days prior to trial entry
- Receipt of live vaccines within 30 days prior to treatment
- Confirmation that none of the trial registration exclusion criteria apply at trial entry
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 6 locations
1
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom, BH7 7DW
Not Yet Recruiting
2
King's College Hospital
London, England, United Kingdom, SE5 9RS
Actively Recruiting
3
Christie Hospital NHS Trust
Manchester, England, United Kingdom, M20 4BX
Not Yet Recruiting
4
Velindre Cancer Center at Velinde Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Actively Recruiting
5
Guy's and St Thomas' Hospital NHS Foundation Trust
London, United Kingdom, SE1 9RT
Actively Recruiting
6
Weston Park Hospital
Sheffield, United Kingdom
Not Yet Recruiting
Research Team
C
Christophe Verstegen
CONTACT
M
Michelle Frost
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
OTHER
Number of Arms
7
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