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

Recruiting

• Conditions: Breast Cancer Stage I; Triple Negative Breast Cancer (TNBC)
• Interventions: Other: No adjuvant chemotherapy; Drug: Adjuvant chemotherapy

• Registration Number: NCT06476119
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-07
• Study First Submitted QC: 2024-06-20
• Study First Posted: 2024-06-26
• Status Verified: 2025-04
• Study Start: 2025-04-15
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-23
• Primary Completion: 2032-09-15
• Study Completion: 2034-09-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 490

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Optimisation cohort	No adjuvant chemotherapy	patients will be treated with surgery and adjuvant radiotherapy following local/national guidelines, while chemotherapy will be omitted
Control cohort	Adjuvant chemotherapy	patients will be treated with surgery, adjuvant radiotherapy and adjuvant chemotherapy following local/national guidelines

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (28)

Zuyderland Medisch Centrum; 🇳🇱 Sittard-Geleen, Limburg, Netherlands

Flevoziekenhuis; 🇳🇱 Almere, Netherlands

Medical spectrum Twente; 🇳🇱 Enschede, Overijssel, Netherlands

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

Meander Medisch Centrum; 🇳🇱 Amersfoort, Netherlands

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

Onze Lieve Vrouwe Gasthuis (OLVG); 🇳🇱 Amsterdam, Netherlands

Rijnstate; 🇳🇱 Arnhem, Netherlands

Amphia ziekenhuis; 🇳🇱 Breda, Netherlands

Haaglanden Medisch Centrum; 🇳🇱 Den Haag, Netherlands

Deventer Ziekenhuis; 🇳🇱 Deventer, Netherlands

Ziekenhuis Gelderse Vallei; 🇳🇱 Ede, Netherlands

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Jeroen Bosch ziekenhuis; 🇳🇱 Eindhoven, Netherlands

St. Jansdal; 🇳🇱 Harderwijk, Netherlands

Ziekenhuisgroep Twente; 🇳🇱 Hengelo, Netherlands

Tergooi ziekenhuizen; 🇳🇱 Hilversum, Netherlands

Spaarne Gasthuis; 🇳🇱 Hoofddorp, Netherlands

Dijklander ziekenhuis; 🇳🇱 Hoorn, Netherlands

MCL; 🇳🇱 Leeuwarden, Netherlands

LUMC; 🇳🇱 Leiden, Netherlands

MUMC; 🇳🇱 Maastricht, Netherlands

St. Antonius ziekenhuis; 🇳🇱 Nieuwegein, Netherlands

Radboud UMC; 🇳🇱 NIjmegen, Netherlands

Erasmus Medical Center Cancer Institute; 🇳🇱 Rotterdam, Netherlands

Franciscus Gasthuis & Vlietland; 🇳🇱 Schiedam, Netherlands

VieCuri Medisch Centrum voor Noord-Limburg; 🇳🇱 Venlo, Netherlands

Isala; 🇳🇱 Zwolle, Netherlands