SPatial Heterogeneity of INtratumoral drug distribution

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-07-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Determine the spatial distribution of Aromatase Inhibitor and CDK4/6 inhibitor (ribociclib) in ER+ HER2- early breast cancer in postmenopausal patients scheduled to undergo upfront surgery for their tumor.

Secondary objectives 1

1. Characterize physical tumor properties at different length scales and identify spatially distinct regions with similar physiologies (habitats) - Correlate (patterns of) drug distribution to tumor properties (habitats) and the relation to treatment outcome. - Investigate the immune modulatory effects of AI +/- ribociclib on the frequency and differentiation/activation state of effector T cells, Tregs and myeloid (including dendritic cell) subsets – in the SLN, in PBMCs and primary tumor. - Relation of response in primary tumor to AI +/- ribociclib including immunemodulatory effects - Safety of AI + ribociclib up to surgery

Conditions and MedDRA coding

ER+ HER2- Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Adult postmenopausal women (≥ 18 years of age). Men will not be able to participate as there is no registration for treatment with aromatase inhibition in early breast cancer. 2.Pathologically proven diagnosis of adenocarcinoma of the breast with clinical stage I-IIa (clinical stage T1c-T2N0; tumors of 1.5-5 cm) scheduled for upfront surgery 3.Documentation of histologically confirmed diagnosis breast cancer with ER expression ≥10% and HER2 negative according to standard procedures based on local results. 4.Good performance status, ECOG>2 5. Good organ function. 6.Able to give written informed consent and to comply with the SPHINX protocol.

Exclusion criteria 1

1. 1.Contra-indication for aromatase inhibitors (AI). 2.Contra-indication for ribociclib a. Prolonged QTc time of ≥ 450 ms b. Allergy to peanuts/soja (coating ribocliclib tablets) 3.Contra-indication for MRI imaging. 4. Contra-indications for US contrast agent 5. Prior endocrine therapy or chemotherapy for breast cancer 6.Use of hormone replacement therapy 7.Patients should have no other current malignancy except squamous cell skin cancer of basal cell skin cancer. 8.Patients cannot have had exposure <12 months to the use of AI and/or CDK4/6 inhibitors.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Concentration of AI and CDK4/6 inhibitor (ribociclib) in different regions of the tumor tissue using mass spectrometry.

Secondary endpoints 9

1. Characterization of both anatomical and functional spatial variations in the tumor microenvironment at the macroscopic level using magnetic resonance imaging (MRI) and Ultrasonography (US)
2. Characterization of anatomical spatial variations in the tumor microenvironment at the microscopic scale using immunohistochemistry (IHC)
3. Delineation of tumor habitats at macro- and microscopic level based on multimodality and multiparametric imaging
4. Immune subset frequencies and activation state in SLN and in peripheral blood by flow cytometry, at baseline and on treatment with AI +/- ribociclib
5. T cell functionality in SLN tested by cytokine release upon polyclonal stimulation
6. Cytokine/chemokine profiling performed on plasma samples
7. Immune effects of the treatment at the primary tumor site assessed by IHC
8. - (severe) adverse events due to ribociclib (according to criteria of common terminology for adverse events (CTCAE) 5.0 scored up to 30 days after surgery)
9. Response to CDK4/6 inhibition + AI in primary tumor measured by - residual cancer burden (RCB) - Ki67 expression assessed by IHC

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

C. W. Menke-van der Houven van Oordt

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

C. W. Menke-van der Houven van Oordt

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications