Phase
Condition
Breast Cancer
Cancer
Treatment
Avelumab
Lansoprazole
Aspirin
Clinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Written informed consent, willing and able to comply with the trial protocol for theduration of the trial including all treatments and scheduled biopsies.
Female patients, age 18 and over
Histologically confirmed triple negative invasive breast cancer as defined asoestrogen receptor (ER) negative, progesterone receptor (PgR) negative (ifavailable, otherwise PgR unknown), (as defined by Allred score 0- 2 or <1% of tumourcells positive for stain) and HER2 negative (immunohistochemistry 0/1+ or negativeby in situ hybridization) as determined by local laboratory. Have previouslyuntreated, nonmetastatic TNBC with a tumour amenable to multiple biopsies includinga T stage of at least T2. Note multifocal primary tumours are allowed providing atleast one tumour meets the criteria above. All biopsies should be obtained from thesame tumour.
Have previously untreated, non-metastatic TNBC with a tumour amenable to multiplebiopsies including a T stage of at least T2. Note multifocal primary tumours areallowed providing at least one tumour meets the criteria above. All biopsies shouldbe obtained from the same tumour.
ECOG performance status 0/1
Women of childbearing potential (WOCBP), defined as not surgically sterilized or notpost-menopausal for at least 24 months if age ≤55 years or 12 months if age >55years, must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 14 days prior to the start of either IMPstudy treatment (Avelumab, and Aspirin if applicable).
Adequate organ function:
Adequate Hepatic function:
- AST and ALT <2.5x ULN
- Alkaline phosphatase ≤2 x ULN
- Total Bilirubin within normal range i.e. ≤1.5 x ULN. If AST/ ALT andAlkaline phosphatase are within normal limits then isolated elevation ofbilirubin to 3≤ ULN and a presumptive diagnosis of Gilbert's syndrome ispermitted.
- Adequate organ function as defined by:
- Bone marrow function: Hb ≥100g/L
- Absolute neutrophil count ≥1.5 x 109/L
- Platelets ≥100 x 109/L
- Hemoglobin >9 g/dL
- Renal function: Creatinine ≤1.5 x ULN OR > 50ml/min using theCockcroft-Gault formula (appendix 4).
Exclusion
Exclusion Criteria:
Patients meeting any of the following criteria must not be enrolled in the study:
Prior systemic anti-cancer treatment (immune therapy, targeted therapy, vaccinetherapy, or investigational treatment) for triple negative breast cancer.
Current use of a prohibited medication as described in section 7.11.
Malignancy within the last 5 years except: adequately treated nonmelanoma skincancer; curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS); stage 1, grade I endometrial carcinoma.
Has received a live vaccine within 30 days of the first dose of study treatment. NBSeasonal influenza vaccines are generally inactivated flu vaccines and are allowed;intranasal influenza vaccines (eg FluMist®) are live attenuated vaccines and are notallowed.
Contraindications to aspirin dosing including hypersensitivity to aspirin (eg knownaspirin sensitive asthma; history of peptic ulcer disease, gastric bleeding orcerebrovascular haemorrhages; haemorrhagic diathesis.
Evidence of distant metastases apparent prior to randomisation. Patients who arediagnosed with distant metastases during the course of the study can complete studyprocedures if willing to do so.
Significant cardiovascular disease including a history of myocardial infarction,acute coronary syndrome or coronary angioplasty/stenting/ bypass grafting within thelast 6 months or clinically significant congestive heart failure.
Any other serious or unstable pre-existing medical conditions (aside from malignancyexceptions specified above), psychiatric disorders, or other conditions that in theopinion of the investigator could interfere with the patient's safety, obtaininginformed consent, or compliance with study procedures.
Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis CVirus (HCV) infection (patients with laboratory evidence of cleared or chronic (notactive) HBV and HCV infection will be permitted).
Patients with active, known or suspected autoimmune disease. Patients with type 1diabetes mellitus, hypothyroidism only requiring hormone replacement, skin orrheumatological disorders (such as vitiligo, psoriasis, rheumatoid arthritis oralopecia) not requiring systemic treatment, or conditions not expected to recur inthe absence of an external trigger will be permitted to enrol. Autoimmune conditionssuch as ulcerative colitis that have been definitively treated (e.g. with totalcolectomy) will be permitted to enrol but should be discussed with the CI.
Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenalreplacement steroid doses > 10 mg daily prednisone equivalent are permitted in theabsence of active autoimmune disease.
Patients with interstitial lung disease that is symptomatic or may interfere withthe detection or management of suspected drug-related pulmonary toxicity.
Patients unable to swallow orally administered medication and patients withgastrointestinal disorders likely in to interfere with absorption of the trialmedication.
Females who are pregnant or breast-feeding.
Active infection requiring systemic treatment.
Current or previous regular use of aspirin (at any dose) or current use of anotherNSAID for any indication (see appendix IV for list of medications not permitted inthe trial). Regular aspirin use is defined as taking aspirin more than twice in anygiven week for more than 4 consecutive weeks. Current NSAID use is defined as takingany NSAID for more than a week in the preceding month. If investigators feel thatthis definition may unfairly exclude a participant, this can be discussed with theCI/MCTU and a case by case decision will be made.
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugschemically related to the study treatments.