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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.
Full description
Cohorts A-D have been formally closed for recruitment since 06 August 2024.
Enrollment
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Inclusion and exclusion criteria
Inclusion Criteria for Trial Registration:
Post-menopausal is defined by at least one of the following criteria:
Exclusion Criteria for Trial Registration:
Definitive evidence of metastatic disease (axillary lymph nodes or internal mammary node involvement will not be regarded as evidence of metastatic disease) ;
Patients with bilateral tumours.
History of another primary malignancy within the last 5 years prior to Trial Registration, except for:
Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML;
Severe concurrent disease, infection or co-morbidity that, in the judgment of the local Investigator, would make the patient inappropriate for Trial Registration;
Resting ECG indicating uncontrolled, potentially irreversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >470 msec, electrolyte disturbances, etc.), or patients with congenital long QT syndrome;
Patients unable to swallow orally administered medication;
Patients receiving therapeutic anti-coagulation treatment (including warfarin and novel oral anti-coagulants).
Patients with gastrointestinal disorder affecting absorption (e.g. gastrectomy, active peptic ulcer disease within last 3 months);
History of seizure or any condition that may predispose to seizure.
Other non-malignant systemic disease that would preclude trial treatment or would prevent required follow-up;
Pregnant or breast-feeding;
Prior exposure to PARP inhibitor, including olaparib, anti-PD-1 or anti-PDL1 immunotherapy (including durvalumab) except for pembrolizumab if received as standard of care in combination with neoadjuvant chemotherapy;
Any other disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that in the investigators opinion would cause reasonable suspicion of a disease or condition, that contraindicates the use of trial treatment, that may increase the risk associated with trial participation, that may affect the interpretation of the results, or that would make this trial inappropriate for the patient;
Patients with a known hypersensitivity to pembrolizumab, durvalumab or olaparib or any excipients of the products;
Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT);
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 (HBV; known positive HBV surface antigen (HBsAg) result), hepatitis C (HCV), or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA;
Inclusion Criteria for Trial Entry:
Signed Informed Consent Form (ICF) for Trial Entry;
Residual disease is confirmed as at least one viable disease focus ≥1cm on trial-specific imaging performed at least 1 week following day 1 of the final cycle of NACT.
Provision of acceptable archival diagnostic tumour tissue sample prior to Trial Entry as defined in the Investigator Laboratory Manual.
Recovery from all acute adverse events of prior NACT or pembrolizumab to baseline or NCI CTCAE Grade ≤1, except for alopecia. Patients with irreversible toxicity not reasonably expected to be exacerbated by trial treatment may be included only after consultation with the CI or Coordinating Investigator.
Patients must have adequate haematological, renal and hepatic function as defined by:
Women of childbearing potential must have a confirmed menstrual period and a negative urinary or serum pregnancy test prior to Trial Entry. This should be repeated as applicable to ensure a negative pregnancy test is performed on the day of planned trial treatment.
Confirmation that all Trial Registration inclusion criteria listed in Section 5.3.1 remain satisfied.
Exclusion Criteria for Trial Entry:
Primary purpose
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119 participants in 7 patient groups
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Central trial contact
Michelle Frost; Christophe Verstegen
Data sourced from clinicaltrials.gov
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