Breast CancerEarly Phase 1AteBrONCT04630210

Investigating Atezolizumab in Newly Diagnosed ER Positive Breast Cancer Patients According to Their AdipOsity

A Early Phase 1 study testing Letrozole and Atezolizumab in people with Breast Cancer, run by Universitaire Ziekenhuizen KU Leuven.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years, women only
Conditions the study is for: Breast Cancer
What is being tested?: Letrozole and Atezolizumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: Feb 2021to 31 Jan 2025
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Be willing and able to provide written informed consent for the trial.
Postmenopausal status and ≤75 years of age on day of signing the informed consent with postmenopausal status defined as one of the following: prior bilateral surgical oophorectomy; age ≥ 56 years and natural amenorrhea with ≥1 year since last menses; age <56 years with amenorrhea ≥1 year and serum oestradiol levels and follicle-stimulating hormone (FSH) levels in the postmenopausal range without the use of luteinizing hormone releasing hormone agonists; or age <56 years after hysterectomy with one or both ovaries left in place and serum oestradiol levels and FSH levels in the postmenopausal range.
Be willing to provide tissue from a newly obtained core or excisional biopsy of the tumour that should be evaluable for central histological characterization and future molecular testing.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Have a newly diagnosed non-metastatic previously untreated and operable primary invasive carcinoma of the breast that meets the following criteria: (1) histologically confirmed invasive carcinoma of the breast; (2) invasive carcinoma of no special type (commonly referred to as invasive ductal histology); (3) ER positive/HER2-negative status; (4) proliferation marker Ki67 level of ≥20%; and (5) tumour size on imaging larger than or equal to 1.5 cm (largest diameter). Multifocal, multicentric unilateral or bilateral breast tumours are allowed provided that all routinely collected/analysed foci correspond to all criteria above.
Any clinical nodal status.

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Be willing to provide plasma/blood and tumour samples for translational research.
Demonstrate adequate organ function as defined in Table 2.
Have a negative hepatitis B surface antigen (HBsAg) test at screening.
Have a negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
Have a negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
Completion of all necessary screening procedures within 28 days prior to randomisation.

Who cannot join

Having received any previous systemic anti-cancer treatment (i.e. neoadjuvant) including, but not limited to, chemotherapy, targeted therapy, immunotherapy, hormonal therapy, or having received radiotherapy for the currently diagnosed breast cancer.
Having received hormone replacement therapy or hormonal contraception less than 1 month prior to inclusion.
Currently participating in an interventional study and receiving study therapy or having participated in a study of an investigational agent and having received study therapy or to have used an investigational device within 4 weeks of receiving the treatment dose.
Having a diagnosis of immunodeficiency or having received high-dose systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to receiving the trial treatment. Please note the following exceptions: acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) is allowed; patients who received mineralocorticoids (e.g., fludrocortisone), or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study; and patients who are on treatment with inhalation corticosteroids are eligible for the study.
Known history of TB (Bacillus Tuberculosis) infection.
Known hypersensitivity to atezolizumab or any of its excipients.

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History of severe anaphylactic reaction to chimeric or humanized antibodies or fusion proteins.
Known allergy or hypersensitivity to any component of the letrozole formulation.
History of invasive breast cancer prior to this diagnosis (relapse/second primary).
Personal history of any other malignancy within 5 years prior to inclusion. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy, and in situ cervical carcinoma.
Personal history of autoimmune disease that has required systemic treatment as follows: treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to study inclusion; or treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to study inclusion, or anticipation of need for systemic immunosuppressive medication during study treatment. Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: rash must cover <10% of body surface area, disease must be well controlled at baseline and may require only low-potency topical corticosteroids, no occurrence of acute exacerbations of the underlying condition requiring psoralen and ultraviolet A (PUVA) therapy or ultraviolet B (UVB) therapy, radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency oral corticosteroids within the previous 12 months.
To have a history of pulmonary fibrosis, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis. History of radiation induced lung injury such as radiation pneumonitis or radiation fibrosis is permitted.
To have a recent or active infection that requires or has required systemic therapy, being either: a severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to bacteremia, or severe pneumonia; a severe infection within 4 weeks prior to initiation of study treatment that has required hospitalization because of its complications, or an infection that has been treated with oral or IV antibiotics, antiviral treatment, systemic antimycotics or systemic antiparasitic drugs within 1 week prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
To have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
To have received prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
To have a known history of Human Immunodeficiency Virus (HIV) infection.
To have received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed.
Uncontrolled or symptomatic hypercalcemia.
Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure other than for the breast during the study.
Prior allogeneic stem cell or solid organ transplantation.
To have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

About this study

Official title: Investigating Atezolizumab in Newly Diagnosed Endocrine Receptor Positive Breast Cancer Patients According to Their AdipOsity (AteBrO)

One out of 8 women will develop breast cancer (BC) in her lifetime and despite improvements in therapeutic strategies it remains one of the main causes of cancer-related mortality for women in industrialized countries. Over the past decades another worldwide health problem has emerged: obesity. Around 50% of European women are either overweight or obese (body mass index (BMI)≥25 kg/m2: overweight; BMI≥30 kg/m2: obese). The global health effects of high BMI include the well-known elevated risk for developing cardiovascular disease and diabetes and a broad range of cancers, including in the breast.

The connection between BC and obesity is gaining attention because of its clinical relevance. Heavier BC patients are generally older and tend to present with more aggressive disease (larger tumours and more frequent axillary lymph node dissemination). Likewise, they are also at higher risk of recurrence and resistance to therapy. This is of high importance, as development of therapy-resistant metastases is the ultimate cause of death in relapsing patients. Several molecular pathways linking the more aggressive BC nature to obesity have been proposed, such as oestrogens and fat cell signalling molecules, insulin signalling, metabolic inflammation and altered lipid metabolism.

Adiposity is hardly taken into consideration in the treatment of BC patients. This is in contrast with the emerging trend to develop personalized therapies based on individual characteristics of the patient and molecular features of the tumour. Very recent data show that the upcoming treatment strategy of immunotherapy (IT) has better outcomes in obese patients in melanoma, renal cell and lung carcinoma. This could be explained by the fact that obesity induces T-cell dysregulation, which makes these patients more sensitive to IT. Whether or not this accounts for BC as well, is currently unknown. In endocrine BC treatment, research on the effect of BMI on treatment resistance is mainly retrospective and it is unclear whether heavier patients would present a differential benefit to aromatase inhibitors compared to lean patients. Also, most of these studies only considered BMI and no additional adiposity-related inflammation and other variables.

Here, we therefore want to prospectively evaluate the local and systemic effects of aromatase inhibition and immunotherapy, either combined or alone, in a window of opportunity study carried out in luminal B like postmenopausal BC patients.

Conditions: Breast Cancer
Being tested: Letrozole, Atezolizumab
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LetrozoleDrug
Letrozole 2.5 mg/day oral until surgery
AtezolizumabDrug
Atezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery

Study groups in NCT04630210
Study group	Role	What they receive
A: Letrozole	Experimental	Letrozole 2.5 mg/day oral until surgery Receives: Drug: Letrozole
B: Letrozole + atezolizumab	Experimental	Letrozole 2.5 mg/day oral until surgery and Atezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery Receives: Drug: Letrozole; Drug: Atezolizumab
C: Atezolizumab	Experimental	Atezolizumab 840 mg IV single-dose 14 days (+/- 4 days) before surgery Receives: Drug: Atezolizumab
D: Observation	No intervention	Observation until surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

Ki67 decrease
To detect a decrease in Ki67 expression levels at the time of surgery for obese and overweight postmenopausal luminal B like treatment-naïve early BC patients preoperatively having received a single dose of atezolizumab in combination with letrozole daily (arm B) versus letrozole daily alone (arm A).
Measured: At surgery
sTIL increase
To detect a stronger increase in stromal Tumour Infiltrating Lymphocytes (sTIL) at the time of surgery compared to the time of pre-treatment biopsy for obese and overweight postmenopausal luminal B like treatment-naïve early BC patients preoperatively having received a single dose of atezolizumab, either alone (arm C) or in combination with letrozole daily (arm B) versus letrozole daily alone (arm A).
Measured: At surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 202131 Jan 2025

First posted16 Nov 2020
Study startFeb 2021 (estimated)
Primary completion31 Jan 2025 (estimated)
Study completion31 Jan 2025 (estimated)

Why it stopped: Insufficient resources

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04630210
Sponsor's protocol ID: S63893
Acronym: AteBrO
Status last verified: May 2022
First submitted: 9 Nov 2020
Last updated: 15 Jun 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
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RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
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Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Investigating Atezolizumab in Newly Diagnosed Endocrine Receptor Positive Breast Cancer Patients According to Their AdipOsity (AteBrO)
ClinicalTrials.gov ID: NCT04630210
Acronym / sponsor ID: AteBrO / S63893
Conditions: Breast Cancer
Phase: Early Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Insufficient resources
Enrolment: 0 participants (actual)
Lead sponsor: Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
Collaborators: KU Leuven
Study start: Feb 2021 (estimated)
Primary completion: 31 Jan 2025 (estimated)
Study completion: 31 Jan 2025 (estimated)
First posted: 16 Nov 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
A: Letrozole	Experimental	Drug: LetrozoleLetrozole 2.5 mg/day oral until surgery
B: Letrozole + atezolizumab	Experimental	Drug: Letrozole, Drug: AtezolizumabLetrozole 2.5 mg/day oral until surgery and Atezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery
C: Atezolizumab	Experimental	Drug: AtezolizumabAtezolizumab 840 mg IV single-dose 14 days (+/- 4 days) before surgery
D: Observation	No intervention	–Observation until surgery

Who may qualify

Ages: 18 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Be willing and able to provide written informed consent for the trial.
Postmenopausal status and ≤75 years of age on day of signing the informed consent with postmenopausal status defined as one of the following: prior bilateral surgical oophorectomy; age ≥ 56 years and natural amenorrhea with ≥1 year since last menses; age <56 years with amenorrhea ≥1 year and serum oestradiol levels and follicle-stimulating hormone (FSH) levels in the postmenopausal range without the use of luteinizing hormone releasing hormone agonists; or age <56 years after hysterectomy with one or both ovaries left in place and serum oestradiol levels and FSH levels in the postmenopausal range.
Be willing to provide tissue from a newly obtained core or excisional biopsy of the tumour that should be evaluable for central histological characterization and future molecular testing.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Have a newly diagnosed non-metastatic previously untreated and operable primary invasive carcinoma of the breast that meets the following criteria: (1) histologically confirmed invasive carcinoma of the breast; (2) invasive carcinoma of no special type (commonly referred to as invasive ductal histology); (3) ER positive/HER2-negative status; (4) proliferation marker Ki67 level of ≥20%; and (5) tumour size on imaging larger than or equal to 1.5 cm (largest diameter). Multifocal, multicentric unilateral or bilateral breast tumours are allowed provided that all routinely collected/analysed foci correspond to all criteria above.

Key exclusion criteria (24 listed)

Having received any previous systemic anti-cancer treatment (i.e. neoadjuvant) including, but not limited to, chemotherapy, targeted therapy, immunotherapy, hormonal therapy, or having received radiotherapy for the currently diagnosed breast cancer.
Having received hormone replacement therapy or hormonal contraception less than 1 month prior to inclusion.
Currently participating in an interventional study and receiving study therapy or having participated in a study of an investigational agent and having received study therapy or to have used an investigational device within 4 weeks of receiving the treatment dose.
Having a diagnosis of immunodeficiency or having received high-dose systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to receiving the trial treatment. Please note the following exceptions: acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) is allowed; patients who received mineralocorticoids (e.g., fludrocortisone), or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study; and patients who are on treatment with inhalation corticosteroids are eligible for the study.
Known history of TB (Bacillus Tuberculosis) infection.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LetrozoleLetrozole 2.5 mg/day oral until surgery	Drug	A: Letrozole, B: Letrozole + atezolizumab
AtezolizumabAtezolizumab 840 mg intravenous (IV) single-dose 14 days (+/- 4 days) before surgery	Drug	B: Letrozole + atezolizumab, C: Atezolizumab

Primary outcome

Ki67 decrease
Time frame: At surgery
To detect a decrease in Ki67 expression levels at the time of surgery for obese and overweight postmenopausal luminal B like treatment-naïve early BC patients preoperatively having received a single dose of atezolizumab in combination with letrozole daily (arm B) versus letrozole daily alone (arm A).
sTIL increase
Time frame: At surgery
To detect a stronger increase in stromal Tumour Infiltrating Lymphocytes (sTIL) at the time of surgery compared to the time of pre-treatment biopsy for obese and overweight postmenopausal luminal B like treatment-naïve early BC patients preoperatively having received a single dose of atezolizumab, either alone (arm C) or in combination with letrozole daily (arm B) versus letrozole daily alone (arm A).

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2022.
Individual participant dataSharing planned: No

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hans Wildiers, MD PhD principal investigator

UZ Leuven

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Letrozole and Atezolizumab in people with Breast Cancer, run by Universitaire Ziekenhuizen KU Leuven.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ki67 decrease (time frame: At surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04630210.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2022.