Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04188119 |
Other study ID # |
CFT / sp123 |
Secondary ID |
2018-004121-8001 |
Status |
Not yet recruiting |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 1, 2023 |
Est. completion date |
May 31, 2025 |
Study information
Verified date |
May 2023 |
Source |
The Christie NHS Foundation Trust |
Contact |
Rebecca Taylor |
Phone |
0161306198 |
Email |
rebecca.taylor123[@]nhs.net |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
TNBC is an aggressive subtype of breast cancer associated with poor survival and new
treatments are needed. A key feature of cancer is its ability to go undetected by the immune
system. Recent developments in cancer research have identified immune checkpoints as a
possible treatment option as they seem to promote an anti-tumour immune response.
Some breast cancers have considerable cancer cell infiltration, which has been associated
with better prognosis. This is where white blood cells have permeated the cancer cell and
infiltrated the infected cell in an attempt to 'cure' the infected cell. Greater
immune-sensitivity is thought to correlate with greater cancer cell infiltration therefore
researchers are looking at ways in which immune-sensitivity can be improved.
One approach is to target inflammation that is known to play a major role in cancer
development and progression. Certain proteins can often be abnormally expressed in many
cancers. In preclinical models the investigators recently demonstrated that the presence of
certain cancer cell-derived proteins is critical for the growth of tumours formed by
melanoma, colorectal and breast mouse cancer cell lines. In the mouse preclinical trials it
indicated that by blocking the cancer cells ability to produce these proteins was associated
with a marked shift in the inflammatory profile. To test this theory, this study will use
aspirin as the chosen protein inhibitor and it is speculated that the addition of aspirin
might enhance the efficacy of the immune checkpoint blockade, avelumab.
TRIAL AIMS & DESIGN
The aim of this trial is to determine whether aspirin enhances the efficacy of avelumab by
promoting a greater anti-cancer immune response. This is a multicentre study recruiting
patients with confirmed TNBC from across four trial sites within the United Kingdom. It is
anticipate that 50 participants will need to be screened in order to successfully enrol 42
patients onto the trial. 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
The estimated duration of participation for a participant is up to 10 weeks. Each subject
will be asked to complete 5 study visits. After successfully completing a Screening Visit
(Visit 1), each eligible subject will attend for a Baseline Visit (Visit 2) and will be
randomly assigned to treatment ARM A or ARM B. As part of the baseline visit subjects will
have their first of two breast tumour biopsies. All subjects will commence their PPI
following the baseline visit, those subjects randomised to ARM B will also commence their
Aspirin at this time. At visit 3 all subjects will receive their Avelumab infusion. At Visit
4 (Follow up Visit A) each subject will undergo their second research biopsy and further
research blood sampling this will be the first of two follow up visits, with Visit 5 (Follow
up Visit B) concluding the patients participation.
Visit windows have been used to aid visit planning in the hope that most research
appointments can take place in line with patients' ordinary care visits so as to reduce any
burden inflicted on the patient.
Adverse events (AEs) and Serious Adverse Events (SAEs) will be collected from the time of
randomisation and will continue to be collected up until Visit 5 (Follow up Visit B). All
post biopsy treatment will be at the discretion of the subject's treating physician per local
standard of care.
PATIENT IDENTIFICATION & SCREENING The study will be conducted as a multi-centre trial
consisting of four NHS secondary care out-paints clinics from across the United Kingdom. Each
site has been chosen for their expertise in oncology and their ability to identify patients
for the trial directly from their clinics with each centre treating between 20 to 40 patients
per annum; this pool of patients will constitute the source of recruitment in the study, PIC
sites may also be used.
Potential participants will be identified by the Principal Investigators multidisciplinary
team following recent diagnosis of TNBC. The multidisciplinary team shall be trained on the
study protocol and required to sign the trial delegation and training log in advance of
working on the trial or identifying participants. Potential participants will have at least
24 hours to read the patient information and decide if they would like to participate in the
study. Participants must have the capacity to provide fully informed consent. Participants
must not participate in any other therapeutic trials whilst on study treatments, however once
all study treatments as specified by trial schema are completed, participation in further
studies will not be affected.
At the screening visits the following data will be collected:
- Informed consent
- Demographics
- Medical history
- Concomitant medication
- Complete Physical examination
- Vital Signs 12-lead Electrocardiograph (ECG)
- ECOG performance status
- Blood tests:
- Biochemistry: AST or ALT, LDH, Alk Phos, total bilirubin, sodium, potassium, urea,
creatinine, total protein, albumin, adjusted calcium
- Haematology: FBC: Hb, Platelets, ANC, WBC, Lymphocytes, basophils, eosinophils
- Thyroid Function: Free T4, TSH
- Urinalysis
- Pregnancy testing
- Optional: Microbiome samples kit dispensation (Stool sample, Saliva sample, Nasal Swab)
- Baseline tumour assessment
BASELINE VISIT
The following assessments will be conducted at the time of this visit:
- Adverse Events
- Concomitant medication
- Vital Signs
- ECOG performance status
- Eligibility
- Randomisation
- Research Bloods (Circulating tumour DNA (CtDNA); Plasma for Cytokine Analysis; PBMC
extraction for immunophenotyping)
- Mid-stream Urine sample for prostaglandin
- Optional: Microbiome samples kit collection (Stool sample, Saliva sample, Nasal Swab)
- Breast Tissue Biopsy
- Pre-treatment dispensation (Arm A: PPI OR Arm B: PPI + aspirin)
- Diary card training and dispensation
- Pre-treatment Reminder Telephone call
TREATMENT & FOLLOW UP VISITS Visit 3: I.V visit
The following assessments will be conducted at the time of this visit:
- Assessment of Adverse Events
- Concomitant medication
- Vital Signs
- *Laboratory tests *(Biochemistry, Haematology and Urinalysis only if screening labs were
>14 day prior to visit 3)
- **Pregnancy testing **(only if screen pregnancy test was >14days prior to day Visit 3)
- Microbiome samples kit dispensation only (Stool, Saliva, Nasal Swab )
- Mid-stream Urine sample for prostaglandin
- Diary card - Pre-treatment compliance check (Arm A: PPI, Arm B: PPI + aspirin)
- Avelumab (10mg/kg i.v.)
Visit 4: Follow up A The following assessments will be conducted at the time of this visit
- Adverse Events
- Concomitant medication
- Research Bloods (CtDNA); Plasma for Cytokine Analysis; Immunophenotyping)
- Microbiome sample kit collection (Stool sample, Saliva sample, Nasal Swab)
- Mid-stream Urine sample for prostaglandin
- Breast Tumour Biopsy
- Diary card - Pre-treatment compliance check (Arm A: PPI, Arm B: PPI + aspirin)
Visit 5: Follow up B The following assessments will be conducted at the time of this visit:
- Adverse Events
- Concomitant medication
- Symptom Directed Physical examination
- Vital Signs (BP, HR, Sp02, Temp)
- ECOG performance status
- Laboratory blood tests
- Biochemistry: AST or ALT, LDH, Alk Phos, total bilirubin, sodium, potassium, urea,
creatinine, total protein, albumin, adjusted calcium
- Haematology: FBC - Hb, Platelets, ANC, WBC, Lymphocytes, basophils, eosinophils
- Thyroid Function: Free T4, TSH
- Urinalysis
- Research Bloods (CtDNA); Plasma for Cytokine Analysis; Immunophenotyping)
SAFETY REVIEW An Independent Trial Steering Committee (TSC) and Data Monitoring Committee
(IDMC) is being formed and will review trial safety data as a combined committee group.
TRANSLATIONAL RESEARCH With consent the following samples will be collected from patients and
held by the Manchester Cancer Research Centre (MCRC) biobank:
- Microbiome samples
- Research blood samples
- Breast Tissue Biopsies
The MCRC biobank holds a generic research tissue bank ethics approval under their HTA license
and will release the samples for relevant research, subject to approval by the Biobank's
Access Committee.