OPTImaL:Optimisation of Treatment for Patients With Low Stage Triple-negative Breast Cancer With High Stromal Tumor-infiltrating Lymphocytes (OPTImaL)

The aim of this study is to investigate whether subjects with breast cancer that have certain favorable features, after performing the surgery and radiation, the chemotherapy can be safely omitted in the treatment. In addition, the investigation looks at whether the omission of chemotherapy ensures a better quality of life. Participants decide, in consultation with their treating physician, whether they choose to be treated with adjuvant chemotherapy or not.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage I; Triple Negative Breast Cancer (TNBC)
• Intervention / Treatment: Other: No adjuvant chemotherapy; Drug: Adjuvant chemotherapy

• Study Type: Observational
• Enrollment (Estimated): 490

Contacts and Locations

• Study Contact: Name: Marleen Kok, MD; Phone Number: +31205129111; Email: m.kok@nki.nl
• Study Contact Backup: Name: Rianne Rolfes, MD; Phone Number: +31205129111; Email: r.rolfes@nki.nl

Study Locations

• Netherlands
  • Alkmaar, Netherlands
    • Not yet recruiting
    • Noordwest Ziekenhuisgroep
    • Contact: S Vrijaldenhoven, MD
  • Almere, Netherlands
    • Not yet recruiting
    • Flevoziekenhuis
    • Contact: S A.L Bartels, MD
    • Contact: S A.L. Bartels, MD
  • Amersfoort, Netherlands
    • Recruiting
    • Meander Medisch Centrum
    • Contact: J M Baas, MD
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • Antoni van Leeuwenhoek
    • Contact: Marleen Kok, MD; Phone Number: 9111 +3120512; Email: m.kok@nki.nl
    • Contact: Ingrid AM Mandjes, MSc; Phone Number: 9111 +3120512; Email: i.mandjes@nki.nl
    • Contact: Marleen Kok, MD
  • Amsterdam, Netherlands
    • Recruiting
    • Onze Lieve Vrouwe Gasthuis (OLVG)
    • Contact: B Flameling, MD
  • Arnhem, Netherlands
    • Recruiting
    • Rijnstate
    • Contact: K Beelen, MD
  • Breda, Netherlands
    • Recruiting
    • Amphia Ziekenhuis
    • Contact: J Heijns, MD
  • Den Haag, Netherlands
    • Recruiting
    • Haaglanden Medisch Centrum
    • Contact: R. Oosterkamp, MD, PhD
  • Deventer, Netherlands
    • Recruiting
    • Deventer Ziekenhuis
    • Contact: L. Kessels, MD, PhD
  • Ede, Netherlands
    • Recruiting
    • Ziekenhuis Gelderse Vallei
    • Contact: M Verstappen, MD
  • Eindhoven, Netherlands
    • Recruiting
    • Catharina Ziekenhuis
    • Contact: R-J Schipper, MD
  • Eindhoven, Netherlands
    • Recruiting
    • Jeroen Bosch Ziekenhuis
    • Contact: J Tol, MD
  • Harderwijk, Netherlands
    • Recruiting
    • St. Jansdal
    • Contact: J A Ropela, MD
  • Hengelo, Netherlands
    • Recruiting
    • Ziekenhuisgroep Twente
    • Contact: E Siemerink, MD
  • Hilversum, Netherlands
    • Recruiting
    • Tergooi ziekenhuizen
    • Contact: A Willemsen, MD
  • Hoofddorp, Netherlands
    • Recruiting
    • Spaarne Gasthuis
    • Contact: B de Valk, MD
  • Hoorn, Netherlands
    • Not yet recruiting
    • Dijklander Ziekenhuis
    • Contact: M M Vleugel, MD
  • Leeuwarden, Netherlands, 8934 AD
    • Not yet recruiting
    • MCL
    • Contact: L Hamming, MD
  • Leiden, Netherlands
    • Not yet recruiting
    • LUMC
    • Contact: J Kroep, MD
  • Maastricht, Netherlands
    • Not yet recruiting
    • MUMC
    • Contact: M de Boer, MD
  • NIjmegen, Netherlands, 6225GA
    • Not yet recruiting
    • Radboud UMC
    • Contact: E Kuip, MD
  • Nieuwegein, Netherlands
    • Recruiting
    • St. Antonius Ziekenhuis
    • Contact: M J Agterof, MD
  • Rotterdam, Netherlands, 3015CE
    • Not yet recruiting
    • Erasmus Medical Center Cancer Institute
    • Contact: A Jager, MD
  • Schiedam, Netherlands
    • Recruiting
    • Franciscus Gasthuis & Vlietland
    • Contact: J.M. Zuetenhorst, dr.
  • Venlo, Netherlands
    • Not yet recruiting
    • VieCuri Medisch Centrum voor Noord-Limburg
    • Contact: E Boon, MD
  • Zwolle, Netherlands
    • Recruiting
    • Isala
    • Contact: A Honkoop, MD
  • Limburg
    • Sittard-Geleen, Limburg, Netherlands, 6162 BG
      • Not yet recruiting
      • Zuyderland Medisch Centrum
      • Contact: F van den Berkmortel, MD
  • Overijssel
    • Enschede, Overijssel, Netherlands, 7500 KA
      • Recruiting
      • Medical spectrum Twente
      • Contact: M Wymenga, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients with pathological stage I TNBC (pT1a/b/cN0) and a high sTIL score (defined as ≥50% for patients ≥40 years; ≥75% for patients <40 years)

Description

Inclusion Criteria:

• Female or male patients;
• >=18 years;
• Written informed consent;
• TNBC (defined as: invasive carcinoma; ER/PR expression 0-9%; Human Epidermal Growth Factor Receptor 2 [HER2] negative [0, 1+ or 2+ on immunohistochemistry, without HER2 amplification on in-situ hybridization]) on the diagnostic biopsy and the surgical specimen;

• Pathological stage I TNBC (according to the TNM staging 8th edition):

  • pT1a/b/c (≤2 cm), confirmed by an invasive component of ≤2 cm on the surgical specimen (microinvasive disease [pT1mi, ≤1 mm) is not allowed);
  • pN0, confirmed by absence of malignant cells in the sentinel lymph node or any other lymph node after surgery (isolated tumor cells [N0(i+)] are not allowed);
• No evidence of nodal or distant metastases (cN0M0) on pre and/or postoperative imaging examinations (performed following local/national guidelines, but must include an 18F-fluorodeoxyglucose positron emission tomography/computed tomography [18F-FDG-PET/CT, at least from skull base to upper legs] or computed tomography [CT] of neck/chest/abdomen/pelvis [CT only if 18F-FDG-PET/CT would not be available; 18F-FDG-PET/CT mandatory in the Netherlands]);
• sTIL score of ≥50% for patients ≥40 years at the time of TNBC diagnosis and ≥75% for patients <40 years at the time of TNBC diagnosis on an H&E FFPE tissue slide on the surgical specimen, according to International Immuno-Oncology Biomarker Working Group on Breast Cancer (formerly International TILs Working Group) guidelines, by local and central review
• Has undergone curative breast surgery (breast-conserving surgery or mastectomy and surgical axillary staging [including at least sentinel lymph node procedure]);
• Absence of recurrence between curative breast surgery and expression of patient preference;
• Eligible for radiotherapy (if indicated).

Exclusion Criteria:

• Prior disease history of invasive and/or non-invasive breast cancer, or ongoing treatment for invasive and/or non-invasive breast cancer;
• Multifocal, multicentric or bilateral breast cancer at the time of screening;
• Administration of neoadjuvant systemic therapy;
• Presence of lymphovascular invasion on the diagnostic biopsy and/or the surgical specimen;
• Other invasive malignancy within 5 years prior to inclusion, with the exception of ade-quately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤6 prostate cancer;
• Uncontrolled severe illness or medical condition;
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the in the trial.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Optimisation cohort; patients will be treated with surgery and adjuvant radiotherapy following local/national guidelines, while chemotherapy will be omitted	Other: No adjuvant chemotherapy; no adjuvant chemotherapy
Control cohort; patients will be treated with surgery, adjuvant radiotherapy and adjuvant chemotherapy following local/national guidelines	Drug: Adjuvant chemotherapy; adjuvant chemotherapy according to local/ national guidelines; Other Names: according to local/ national guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease recurrence Free Interval (DRFI) - optimalisation cohort per-protocol population	Number of patients with distant recurrence or death in per-protocol population of the optimisation cohort	up to 96 months after inclusion of the last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive disease-free survival (IDFS) - control cohort	Number of patients with breast tumor recurrence or death in the control cohort	up to 96 months after inclusion of the last patient
disease recurrence free survival (DRFS) - control cohort	time between inclusion and first distant recurrence or death from any cause in the control cohort	up to 96 months after inclusion of the last patient
Recurrence-free survival (RFS) - control cohort	time between inclusion and invasive ipsilateral breast tumor recurrence, local-regional invasive recurrence, distant recurrence or death from any cause in the control cohort;	up to 96 months after inclusion of the last patient
Overal Survival (OS) - control cohort	time between inclusion and death from any cause in the control cohort;	up to 96 months after inclusion of the last patient
Fear of recurrence	Assessed with questionnaires to determine the difference in optimisation and control group	up to 2 years after inclusion
Cost effectiveness measured by quality-adjusted-life years (QALYs)	Measured per Quality-Adjusted Life Years (QALYs)	up to 2 years after inclusion
Cost effectiveness measured per incremental cost-effectiveness ratio (ICER)	Measured per incremental cost-effectiveness ratio (ICER)	up to 2 years after inclusion
Disease recurrence Free Interval (DRFI) - optimalisation cohort intention to treat population	Number of patients with distant recurrence or death in intention to treat population of the optimisation cohort	up to 96 months after inclusion of the last patient
Disease recurrence Free Interval (DRFI) - control cohort	Number of patients with distant recurrence or death in control cohort	up to 96 months after inclusion of the last patient
Invasive disease-free survival (IDFS) - optimalisation cohort per-protocol population	Number of patients with breast tumor recurrence or death in the per-protocol population of the optimisation cohort	up to 96 months after inclusion of the last patient
Invasive disease-free survival (IDFS) - optimalisation cohort intention-to-treat population	Number of patients with breast tumor recurrence or death in the the intention-to-treat population of the optimisation cohort	up to 96 months after inclusion of the last patient
disease recurrence free survival (DRFS) - optimalisation cohort per-protocol population	time between inclusion and first distant recurrence or death from any cause in the per-protocol population of the optimisation cohort	up to 96 months after inclusion of the last patient
disease recurrence free survival (DRFS) - optimalisation cohort the intention-to-treat population	time between inclusion and first distant recurrence or death from any cause in the intention-to-treat population of the optimisation cohort population of the optimisation cohort	up to 96 months after inclusion of the last patient
Recurrence-free survival (RFS) - optimalisation cohort per-protocol population	time between inclusion and invasive ipsilateral breast tumor recurrence, local-regional invasive recurrence, distant recurrence or death from any cause in the per-protocol population of the optimisation cohort;	up to 96 months after inclusion of the last patient
Recurrence-free survival (RFS) - optimalisation cohort the intention-to-treat population	time between inclusion and invasive ipsilateral breast tumor recurrence, local-regional invasive recurrence, distant recurrence or death from any cause in the the intention-to-treat population of the optimisation cohort;	up to 96 months after inclusion of the last patient
Overal Survival (OS) - optimalisation cohort per-protocol population	time between inclusion and death from any cause in the per-protocol population of the optimisation cohort;	up to 96 months after inclusion of the last patient
Overal Survival (OS) - optimalisation cohort intention-to-treat population	time between inclusion and death from any cause in the the intention-to-treat population of the optimisation cohort;	up to 96 months after inclusion of the last patient
Health related Quality of Life (HRQoL) - (European Organisation on Research and Treatment of Cancer) EORTC questionnaire QLQ-C30	Difference in QoL assessed with the EORTC QLQ-C30 questionnaires between the optimisation and the control group. A higher score indicates a higher symptom burden.	up to 2 years after inclusion
Health related Quality of Life (HRQoL) - (European Organisation on Research and Treatment of Cancer) EORTC questionnaire QLQ-BR45	Difference in QoL assessed with the EORTC QLQ-BR45 questionnaires between the optimisation and the control group. A higher score indicates a higher symptom burden.	up to 2 years after inclusion
Worries about health	Assessed with questionnaires to determine the difference in optimisation and control group. A higher score indicates a higher symptom burden.	up to 2 years after inclusion

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Maarten van de Weijden Foundation; AVL Foundation
• Investigators: Principal Investigator: Marleen Kok, MD, Antoni van Leeuwenhoek

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): September 15, 2032
• Study Completion (Estimated): September 15, 2034

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: High (stromal Tumor-Infiltrating-Lymphocytes) sTIL score
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: M24OTI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no IPD plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No