Clinical trial NCT06476119: OPTImaL:Optimisation of Treatment for Patients With Low Stage Triple-negative Breast Cancer With High Stromal Tumor-infiltrating Lymphocytes
Official title: OPTImaL:Optimisation of Treatment for Patients With Low Stage Triple-negative Breast Cancer With High Stromal Tumor-infiltrating Lymphocytes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer Stage I
Triple Negative Breast Cancer (TNBC)
Keywords: High (stromal Tumor-Infiltrating-Lymphocytes) sTIL score
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Maarten van de Weijden Foundation
name: AVL Foundation
First posted: 2024-06-26
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Disease recurrence Free Interval (DRFI) - optimalisation cohort per-protocol population
timeFrame: up to 96 months after inclusion of the last patient
Secondary outcomes:
measure: Disease recurrence Free Interval (DRFI) - optimalisation cohort intention to treat population
timeFrame: up to 96 months after inclusion of the last patient
measure: Disease recurrence Free Interval (DRFI) - control cohort
timeFrame: up to 96 months after inclusion of the last patient
measure: Invasive disease-free survival (IDFS) - optimalisation cohort per-protocol population
timeFrame: up to 96 months after inclusion of the last patient
measure: Invasive disease-free survival (IDFS) - optimalisation cohort intention-to-treat population
timeFrame: up to 96 months after inclusion of the last patient
measure: Invasive disease-free survival (IDFS) - control cohort
timeFrame: up to 96 months after inclusion of the last patient
measure: disease recurrence free survival (DRFS) - optimalisation cohort per-protocol population
timeFrame: up to 96 months after inclusion of the last patient
measure: disease recurrence free survival (DRFS) - optimalisation cohort the intention-to-treat population
timeFrame: up to 96 months after inclusion of the last patient
measure: disease recurrence free survival (DRFS) - control cohort
timeFrame: up to 96 months after inclusion of the last patient
measure: Recurrence-free survival (RFS) - optimalisation cohort per-protocol population
timeFrame: up to 96 months after inclusion of the last patient
measure: Recurrence-free survival (RFS) - optimalisation cohort the intention-to-treat population
timeFrame: up to 96 months after inclusion of the last patient
measure: Recurrence-free survival (RFS) - control cohort
timeFrame: up to 96 months after inclusion of the last patient
measure: Overal Survival (OS) - optimalisation cohort per-protocol population
timeFrame: up to 96 months after inclusion of the last patient
measure: Overal Survival (OS) - optimalisation cohort intention-to-treat population
timeFrame: up to 96 months after inclusion of the last patient
measure: Overal Survival (OS) - control cohort
timeFrame: up to 96 months after inclusion of the last patient
measure: Health related Quality of Life (HRQoL) - (European Organisation on Research and Treatment of Cancer) EORTC questionnaire QLQ-C30
timeFrame: up to 2 years after inclusion
measure: Health related Quality of Life (HRQoL) - (European Organisation on Research and Treatment of Cancer) EORTC questionnaire QLQ-BR45
timeFrame: up to 2 years after inclusion
measure: Fear of recurrence
timeFrame: up to 2 years after inclusion
measure: Worries about health
timeFrame: up to 2 years after inclusion
measure: Cost effectiveness measured by quality-adjusted-life years (QALYs)
timeFrame: up to 2 years after inclusion
measure: Cost effectiveness measured per incremental cost-effectiveness ratio (ICER)
timeFrame: up to 2 years after inclusion
Other outcomes:
Locations:
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum
state: Limburg
city: Enschede
country: Netherlands
facility: Medical spectrum Twente
state: Overijssel
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis (OLVG)
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Breda
country: Netherlands
facility: Amphia ziekenhuis
city: Den Haag
country: Netherlands
facility: Haaglanden Medisch Centrum
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Jeroen Bosch ziekenhuis
city: Harderwijk
country: Netherlands
facility: St. Jansdal
city: Hengelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Hilversum
country: Netherlands
facility: Tergooi ziekenhuizen
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Hoorn
country: Netherlands
facility: Dijklander ziekenhuis
city: Leeuwarden
country: Netherlands
facility: MCL
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: MUMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis
city: NIjmegen
country: Netherlands
facility: Radboud UMC
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Cancer Institute
city: Schiedam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum voor Noord-Limburg
city: Zwolle
country: Netherlands
facility: Isala
Study officials:
affiliation: Antoni van Leeuwenhoek
name: Marleen Kok, MD
role: PRINCIPAL_INVESTIGATOR
References: