A Proof of Concept, Window Trial of the IMmunological Effects of AveLumab and Aspirin in Triple-Negative Breast Cancer

NCT03794596 | Withdrawn Phase 2 DMC

• 4 other identifiers: CFT/sp1232018-004121-8016_DOG02_289017NovCC1079
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This research is being done because the investigators are looking for new and better ways to treat a type of breast cancer called triple negative breast cancer. This type of breast cancer can be more difficult to treat than other types of breast cancer as it does not respond to drugs such as hormonal therapies. One type of treatment that looks promising is immunotherapy using new drugs called immune checkpoint inhibitors. Immune checkpoints help to regulate the immune system and can stop the immune system from attacking cancer cells. Immune checkpoint inhibitors block this 'off-switch' and aim to help the immune system control the cancer. These drugs have been very effective in other cancers such as melanoma and are now being tested in breast cancer. In this study patients will receive an immune checkpoint inhibitor called avelumab. Half the patients on the study will also receive aspirin tablets for approximately 18 days as the investigators wish to compare the effects of avelumab alone versus in combination with aspirin. Patients will attend hospital approximately five times in order to complete all necessary study assessments. The first visit screens patients for suitability, after which a baseline visit will collect the first of two breast tissue biopsies. At the third visit a single dose of Avelumab will be given via an infusion (a drip in the forearm). Patients will then return approximately two weeks later for a second breast tissue biopsy before having a final follow up visit another two weeks later. Blood and urine samples will be taken at various visits throughout the study to help us learn more about the effects these treatments may have on the immune system and on breast cancer cells.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Mean combined gene expression of COX-2 tumour-promoting genes

  Mean combined gene expression of COX-2 tumour-promoting genes, in samples taken post treatment

  7 weeks

Secondary Outcomes (4)

• Post treatment tumour infiltrating lymphocytes (TIL)

  7 weeks

• Mean combined gene expression of the elements of the denominator of the COX-2 ratio

  7 weeks

• The post treatment COX-2 ratio

  7 weeks

• Safety and tolerability assessed by grade 3-4 AEs and SAEs

  7 weeks

Study Arms (2)

(Arm A) Avelumab + PPI

EXPERIMENTAL

21 patients into Arm A: Avelumab + Proton Pump Inhibitor (PPI)

Drug: Avelumab; Drug: Lansoprazole (Proton Pump Inhibitor)

(Arm B) Avelumab + Aspirin + PPI

EXPERIMENTAL

21 patients into Arm B: Avelumab + Aspirin + PPI

Drug: Avelumab; Drug: Aspirin; Drug: Lansoprazole (Proton Pump Inhibitor)

Interventions

Avelumab DRUG

Colourless odourless aqueous solution for infusion at dose of 10mg/kg

Also known as: Bavencio

(Arm A) Avelumab + PPI; (Arm B) Avelumab + Aspirin + PPI

Aspirin DRUG

300mg tablets

(Arm B) Avelumab + Aspirin + PPI

Lansoprazole (Proton Pump Inhibitor) DRUG

300mg capsule

Also known as: Lansoprazole

(Arm A) Avelumab + PPI; (Arm B) Avelumab + Aspirin + PPI

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients, age 18 and over
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent, willing and able to comply with the trial protocol for the duration of the trial including all treatments and scheduled biopsies.
• Female patients, age 18 and over
• Histologically confirmed triple negative invasive breast cancer as defined as oestrogen receptor (ER) negative, progesterone receptor (PgR) negative (if available, otherwise PgR unknown), (as defined by Allred score 0- 2 or \<1% of tumour cells positive for stain) and HER2 negative (immunohistochemistry 0/1+ or negative by in situ hybridization) as determined by local laboratory. Have previously untreated, non-metastatic TNBC with a tumour amenable to multiple biopsies including a T stage of at least T2. Note multifocal primary tumours are allowed providing at least one tumour meets the criteria above. All biopsies should be obtained from the same tumour.
• Have previously untreated, non-metastatic TNBC with a tumour amenable to multiple biopsies including a T stage of at least T2. Note multifocal primary tumours are allowed providing at least one tumour meets the criteria above. All biopsies should be obtained from the same tumour.
• ECOG performance status 0/1
• Women of childbearing potential (WOCBP), defined as not surgically sterilized or not post-menopausal for at least 24 months if age ≤55 years or 12 months if age \>55 years, must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days prior to the start of either IMP study 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 and Alkaline phosphatase are within normal limits then isolated elevation of bilirubin to 3≤ ULN and a presumptive diagnosis of Gilbert's syndrome is permitted.
• 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

You may not qualify if:

• Patients meeting any of the following criteria must not be enrolled in the study:
• Prior systemic anti-cancer treatment (immune therapy, targeted therapy, vaccine therapy, 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 non-melanoma skin cancer; 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.
• NB Seasonal influenza vaccines are generally inactivated flu vaccines and are allowed; intranasal influenza vaccines (eg FluMist®) are live attenuated vaccines and are not allowed.
• Contraindications to aspirin dosing including hypersensitivity to aspirin (eg known aspirin sensitive asthma; history of peptic ulcer disease, gastric bleeding or cerebrovascular haemorrhages; haemorrhagic diathesis.
• Evidence of distant metastases apparent prior to randomisation. Patients who are diagnosed with distant metastases during the course of the study can complete study procedures if willing to do so.
• Significant cardiovascular disease including a history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months or clinically significant congestive heart failure.
• Any other serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that in the opinion of the investigator could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (patients with laboratory evidence of cleared or chronic (not active) HBV and HCV infection will be permitted).
• Patients with active, known or suspected autoimmune disease. Patients with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin or rheumatological disorders (such as vitiligo, psoriasis, rheumatoid arthritis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger will be permitted to enrol. Autoimmune conditions such as ulcerative colitis that have been definitively treated (e.g. with total colectomy) 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 adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely in to interfere with absorption of the trial medication.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• University of Manchester: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

avelumab; Aspirin; Lansoprazole; Proton Pump Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Anne Armstrong

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Laboratory staff and the blinded statistician will remain blinded to trial treatment arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Non CI Project manager

Model Details: Patients will be randomly assigned to one of two arms:- * 21 patients into Arm A: Avelumab + Proton Pump Inhibitor (PPI) * 21 patients into Arm B: Avelumab + Aspirin + PPI

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: January 7, 2019
• Study Start: September 1, 2019
• Primary Completion: February 28, 2021
• Study Completion: February 28, 2021
• Last Updated: July 22, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share