ENDO-67 project: Investigating ENDOcrine therapy-related questions using Ki67 changes in the window-of-opportunity before breast surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-10-21

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacogenomic, Pharmacokinetic

1. Can steady-state levels of endoxifen be achieved within three (rather than twelve) weeks using the PK model-derived tamoxifen loading schedule?
2. Can ER-pathway inactivity, measured by percentage Ki67 before and after treatment in ER positive tumours, reliable predict tamoxifen insensitivity?
3. What is de correlation between intratumoral endoxifen levels and Ki67 response?

Secondary objectives 4

1. What is the concordance between Ki67 percentage measured after three weeks of tamoxifen treatment (biopsy) and the resection specimen?
2. What is the effect of tamoxifen on estradiol and progesterone levels in pre- and postmenopausal women?
3. What is the concordance between Ki67 percentage measured by the pathologist versus an artificial intelligence (AI) algorithm
4. What is the difference in side effects experiences after three weeks using the loading schedule of tamoxifen compared to after 12 weeks of continuous use of 20mg using the FACT-ES questionnaire

Conditions and MedDRA coding

Breast cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with treatment naïve, ≥cT1c ER+, Her2- primary breast cancer (tumor still in situ) with a Ki-67 ≥10%
2. Age older than 18 year
3. An indication for postoperatively endocrine treatment
4. WHO performance status 0-2
5. The primary breast tumor should be amendable for multiple biopsies
6. Specific for tamoxifen: Indication for adjuvant tamoxifen treatment

Exclusion criteria 8

1. Women who are pregnant or breast feeding
2. Patients in whom neoadjuvant chemotherapy is indicated and delay is not desirable
3. Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair treatment compliance
4. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of endocrine treatment or puts the patient at high risk for treatment related complications.
5. Specific for tamoxifen: Endometrial cancer (diagnosis < 3 years ago)
6. Specific for tamoxifen: • Use of strong CYP2D6-inhibitors without the possibility to stop this medication
7. Specific for tamoxifen: • Concomitant use of over-the-counter-drugs, herbal or homeopathic remedies which (may) interfere with tamoxifen and not willing to stop such as (but not limited to ) St. John’s Wort, curcuma/piperine
8. Specific for tamoxifen: Known poor metabolizer of CYP2D6

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Endoxifen levels after three months of continuous use of 20mg (standard dose) of tamoxifen
2. Tamoxifen resistance defined as Ki67 >10% after three weeks of tamoxifen use according to an adequate dosing schedule
3. Intratumoral endoxifen levels after three weeks and Ki67 response defined as difference between Ki67 percentage for and Ki67 percentage after three weeks of tamoxifen according to an adequate dosing schedule

Secondary endpoints 4

1. Ki67 percentages on tumor material
2. Levels on estradiol and progesterone in blood after three weeks and three months of tamoxifen treatment
3. Ki67 percentages on tumor material measured by the pathologist and measured by an AI algorithm
4. Change in scores of the FACT-ES questionnaire

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

M. van Rosmalen

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

M. van Rosmalen

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 5 files

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

Application history

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