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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04188119
Recruitment Status : Not yet recruiting
First Posted : December 5, 2019
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
University of Manchester
Information provided by (Responsible Party):
Rachel Cox, The Christie NHS Foundation Trust

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Avelumab Drug: Aspirin Drug: Lansoprazole Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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
Masking: Single (Outcomes Assessor)
Masking Description: Laboratory staff and the unblinded statistician ill remain blinded to trial treatment
Primary Purpose: Treatment
Official Title: A Proof of Concept Window Trial of the IMmunological Effects of AveLumab and Aspirin in Triple-Negative Breast Cancer
Estimated Study Start Date : March 2, 2020
Estimated Primary Completion Date : August 30, 2021
Estimated Study Completion Date : August 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: (Arm A) Avelumab + Proto Pump Inhibitor (PPI)
21 patients into Arm A: Avelumab + Proton Pump Inhibitor (PPI)
Drug: Avelumab
(Arm A) Avelumab + Proto Pump Inhibitor (PPI)
Other Name: Bavencio

Drug: Lansoprazole
30mg

Experimental: (Arm B) Avelumab + Aspirin + PPI
21 patients into Arm B: Avelumab + Aspirin + PPI
Drug: Avelumab
(Arm A) Avelumab + Proto Pump Inhibitor (PPI)
Other Name: Bavencio

Drug: Aspirin
300mg tablets

Drug: Lansoprazole
30mg




Primary Outcome Measures :
  1. 1. Mean combined gene expression of COX-2 tumour-promoting genes [ Time Frame: 7 weeks ]
    1. Mean combined gene expression of COX-2 tumour-promoting genes, in samples taken post treatment


Secondary Outcome Measures :
  1. Post treatment tumour infiltrating lymphocytes (TIL) [ Time Frame: 7 weeks ]
    Post treatment tumour infiltrating lymphocytes (TIL) assessed by IHC using standardised methodology (Salgado et al., 2015)

  2. Mean combined gene expression of the cancer-inhibitory elements of the COX-2 inflammatory signature [ Time Frame: 7 weeks ]
    Mean combined gene expression of the cancer-inhibitory elements of the COX-2 inflammatory signature, in samples taken post treatment

  3. The post treatment COX-2 inflammatory signature [ Time Frame: 7 weeks ]
    The post treatment COX-2 inflammatory signature

  4. Safety and tolerability assessed by grade 3-4 AEs and SAEs [ Time Frame: 7 weeks ]
    Safety and tolerability assessed by grade 3-4 AEs and SAEs. In addition, grade 2 renal toxicity AEs (creatinine rise) and grade 2 gastrointestinal toxicity AEs (duodenal perforation, dyspepsia, oesophageal haemorrhage, dysphagia, oesophageal pain, oesophageal perforation, oesophagitis)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female patients aged 18 and over
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent, willing and able to comply with the trial protocol for the duration of the trial including all treatments and scheduled biopsies.
  2. Female patients, age 18 and over
  3. 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, nonmetastatic 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.
  4. 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.
  5. ECOG performance status 0/1
  6. 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).
  7. Adequate organ function:

    1. 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.
    2. 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 the Cockcroft-Gault formula (appendix 4).

Exclusion Criteria:

Patients meeting any of the following criteria must not be enrolled in the study:

  1. Prior systemic anti-cancer treatment (immune therapy, targeted therapy, vaccine therapy, or investigational treatment) for triple negative breast cancer.
  2. Current use of a prohibited medication as described in section 7.11.
  3. Malignancy within the last 5 years except: adequately treated nonmelanoma skin cancer; curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS); stage 1, grade I endometrial carcinoma.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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).
  10. 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.
  11. 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.
  12. Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  13. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely in to interfere with absorption of the trial medication.
  14. Females who are pregnant or breast-feeding.
  15. Active infection requiring systemic treatment.
  16. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication (see appendix IV for list of medications not permitted in the trial). Regular aspirin use is defined as taking aspirin more than twice in any given week for more than 4 consecutive weeks. Current NSAID use is defined as taking any NSAID for more than a week in the preceding month. If investigators feel that this definition may unfairly exclude a participant, this can be discussed with the CI/MCTU and a case by case decision will be made.
  17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04188119


Contacts
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Contact: Rachel Cox 0161306198 ext 0161306198 rachel.cox@manchester.ac.uk
Contact: Safia Barber 01613068096 ext 01613068096 safia.barber@manchester.ac.uk

Sponsors and Collaborators
The Christie NHS Foundation Trust
University of Manchester
Investigators
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Principal Investigator: Anne Armstrong The Christie NHS Foundation Trust

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Responsible Party: Rachel Cox, Project Manager, The Christie NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT04188119    
Other Study ID Numbers: CFT / sp123
2018-004121-80 ( EudraCT Number )
017NovCC107 ( Other Grant/Funding Number: Breast Cancer Now )
First Posted: December 5, 2019    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aspirin
Lansoprazole
Antibodies, Monoclonal
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Immunologic Factors
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors