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New treatment option for Breast Neoplasm
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
ClinicalTrials.gov ID: NCT03740893
What this study is testing
What is AZD6738?
AZD6738 is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for breast neoplasm.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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).
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- for Trial Registration:
- Signed Informed Consent Form (ICF) for Trial Registration;
- Aged ≥18 years old;
- Histologically confirmed invasive triple negative breast cancer (TNBC). TNBC defined as ER negative, PgR negative (ER and PgR negative as defined by...
- Planned definitive surgical treatment after at least 6 cycles of neoadjuvant chemotherapy (NACT) Patients currently receiving SOC pembrolizumab, or...
You likely can't join if
- for Trial Registration:
- Definitive evidence of metastatic disease (axillary lymph nodes or internal mammary node involvement will not be regarded as evidence of metastatic...
- Patients with bilateral tumours.
- History of another primary malignancy within the last 5 years prior to Trial Registration, except for:
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
- Adequately treated carcinoma in situ without evidence of disease;
See the full eligibility criteria
Who can join
- for Trial Registration:
- Signed Informed Consent Form (ICF) for Trial Registration;
- Aged ≥18 years old;
- Histologically confirmed invasive triple negative breast cancer (TNBC). TNBC defined as ER negative, PgR negative (ER and PgR negative as defined by Allred score 0/8, 1/8 or 2/8 or stain in \<1% of cancer cells) or PgR...
- Planned definitive surgical treatment after at least 6 cycles of neoadjuvant chemotherapy (NACT) Patients currently receiving SOC pembrolizumab, or having previously received SOC pembrolizumab but subsequently...
- Radiographically measurable tumour mass assessable for new distinct radio-opaque marker insertion and repeated biopsies on the NACT mid-assessment standard of care imaging modality;
- Eastern Oncology Cooperative Group (ECOG) performance status 0-1;
- Considered fit enough to have breast cancer surgery with curative intent;
- Considered fit to complete at least 2 weeks of pre-operative trial treatment in the WOP;
- Patients must be suitable for a mandatory pre-treatment baseline biopsy performed Day -1 or 1 of the window of opportunity (WOP) and a post-treatment biopsy performed on Day 14 of the WOP. Registered patients who are...
- Patients with clinical stage II or III disease or clinical suspicion of metastatic disease must have staging studies to exclude metastatic disease if this is standard of care, and staging methods should be used as per...
- Patients with previous invasive cancers (including breast cancer) are eligible if the treatment was completed \>5 years prior to Trial Registration, and there is no evidence of recurrent disease;
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up schedule; those conditions should be discussed with the patient...
- Patients must be a) surgically sterile (i.e. if female have undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy; if male have undergone a bilateral orchidectomy); b) have a sterilised sole...
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution for women \< 50 years of age not using hormonal contraception or hormonal replacement therapy...
- Radiation-induced oophorectomy with last menses \>1 year ago
- Chemotherapy-induced menopause with \>1 year interval since last menses
- Surgical sterilisation (hysterectomy, bilateral salpingectomy or bilateral oophorectomy)
What rules you out
- 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:
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
- Adequately treated carcinoma in situ without evidence of disease;
- 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...
- 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...
- 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...
- 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...
- Patients must have adequate haematological, renal and hepatic function as defined by:
- Haemoglobin (Hb) ≥ 10 g/dL (≥ 100 g/L) with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 x 109/L)
- Platelet count ≥100,000/mm3 (≥ 100 x 109/L)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional ULN
- Calculated creatinine clearance ≥51 mL/min using the Cockcroft-Gault equation (please refer to Appendix 4) or based on a 24 hour urine test or another validated test as per local practice
- 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...
- Confirmation that all Trial Registration inclusion criteria listed in Section 5.3.1 remain satisfied. Exclusion Criteria for Trial Entry:
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled...
- Major surgery (excluding minor procedures, e.g. placement of vascular access) within 2 weeks prior to Trial Entry. Patients must have recovered from any effects of any major surgery prior to commencing trial treatment.
- Use of any investigational agent within 30 days prior to commencing trial treatment.
- Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or...
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) CYP3A...
- Whole blood infusion within 28 days prior to trial entry (packed red blood cells and platelet transfusions are acceptable).
- Receipt of live attenuated vaccine within 30 days prior to commencing trial treatment.
- Confirmation that none of the Trial Registration exclusion criteria listed in Section 5.3.2 are met.
The study team makes the final eligibility decision.
Where it's taking place
- Bournemouth, Dorset, United Kingdom
- London, England, United Kingdom
- Manchester, England, United Kingdom
- Cardiff, Wales, United Kingdom
- London, United Kingdom
- Sheffield, United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Bournemouth, Dorset, United Kingdom; London, England, United Kingdom; Manchester, England, United Kingdom; Cardiff, Wales, United Kingdom; London, United Kingdom; Sheffield, United Kingdom. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.