PROOFS-Registry - Premenopausal Women With Breast Cancer Optimally Treated With OFS

Female Breast Cancer Clinical Trial

— PROOFS  

Official title:

Real World Data and Long-term FU of Pre-/Perimenopausal Women With Luminal EBC With Intermediate to High Clinical and Low Genomic Recurrence-risk Measured by MammaPrint®, Treated by SOC ET+OFS or SOC Chemotherapy Treatment Followed by ET

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05792150
• Other study ID #: WSG-NIS04 / PROOFS
• Status: Recruiting
• Start date: December 7, 2022
• Est. completion date: June 2035

Study information

• Verified date: September 2023
• Source: West German Study Group
• Contact: Julian Moellers
• Phone: 00492161566 23-0
• Email: julian.moellers[@]wsg-online.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

There is only limited data for premenopausal patients in general, as well as for differences in the use of OFS in the subgroups of pre- and perimenopausal patients, respectively. The WSG ADAPT trial data on the impact of postmenopausal status and/or use of OFS within 3-4 weeks endocrine induction therapy show relevant impact of OFS/postmenopausal status on Ki-67 response; also, secondary amenorrhea after (neo-)adjuvant chemotherapy was a positive predictor of outcome due to OFS [8, 9].

This registry will give insights in the real-world use of OFS and the effect of secondary amenorrhea in female pre- and perimenopausal patients with or without previous use of chemotherapy and with different endocrine treatments (ET +/- GnRH).

As adherence over time (5-10 years) plays a major role in the endocrine treatment, the registry will follow patients' treatments for up to 10 years and include QoL information.

Results of MammaPrint® (MammaPrint® Index) as indicating factor for chemotherapy use and risk classification, thus, choice of adjuvant treatment (chemotherapy, OFS combined with endocrine therapy, or endocrine therapy alone) will be correlated to outcome under real-world conditions.

Baseline, treatment, and relapse data shall be collected to gain further insight in the treatment paths, treatment adherence, and outcome of such patients.

Description:

This registry aims

• to confirm an excellent outcome in pre-/perimenopausal patients treated by endocrine therapy (+ ovarian suppression) in patients with low genomic risk by MammaPrint® without chemotherapy use in a real-world setting.

• to evaluate management of ovarian function in patients treated by adjuvant chemotherapy according to investigator decision.

• to evaluate adherence to endocrine therapy (+/- ovarian function suppression).

• to evaluate the prognostic impact of clinicopathological markers (e.g., estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, Ki-67 at baseline and after preoperative endocrine therapy (if any performed) by local pathology assessment compared to genomic signature result.

• to assess the course of quality of life (QLQ BR23 and QLQ-C30) until 5 years of treatment with OFS (Baseline, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, 5 years)

In general, WSG aim to assess the quality of surveillance care in younger breast cancer patients. WSG want to gain knowledge about endocrine induction treatment for indication of chemotherapy followed by endocrine treatment or endocrine treatment alone. Also, WSG aim at changes in duration of endocrine treatment (especially in high-risk patients up to 10 years) and introduction of intensified endocrine therapy (OFS) in combination with GnRH-analogues since publication of the SOFT and TEXT trials.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1470
• Est. completion date: June 2035
• Est. primary completion date: March 2035
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Patients are eligible for participation in the registry only if they meet all the following criteria:

• Female breast cancer patients

• Pre- or perimenopausal at registry entry (age <60 years and state after hysterectomy or amenorrhea for <12 months; confirmation by blood hormone levels (FSH and estradiol in premenopausal range as per local normal range) recommended)

• Primary tumor diagnosis not older than three months prior to inclusion (primary diagnosis defined as date of initial tumor biopsy)

• Estrogen- and/or progesterone-receptor-positive/HER2 negative early breast cancer without any clinical signs of metastases

• Adequate risk for recurrence:

• intermediate clinical risk for recurrence, defined as (clinical in case of neoadjuvant treatment):

• c/pT1 and

• c/pN0 and

• Ki-67 15-24% or

• G2 or

• patients, who do not meet these criteria but are at intermediate clinical risk for recurrence at investigator decision (e.g., very young age, low expression of hormone receptors, existing co-morbidities, familial cancer burden, etc.) can be included on individual decision basis or

• high clinical risk for recurrence, defined as either (clinical in case of neoadjuvant treatment):

• c/pT2-4 or

• c/pN1 or

• Ki-67 =25% or

• G3

• Low genomic risk of recurrence by MammaPrint® (tested on treatment naïve tumor specimen)

• Luminal-type by BluePrint®

• Treatment according to standard-of-care (e.g., AGO Guidelines) planned or started (until completion of local therapy the latest (including started or completed endocrine induction therapy), started, or planned adjuvant or neoadjuvant treatment)

• Availability of untreated tumor material (core biopsy if preoperative endocrine therapy performed or neoadjuvant treatment intended or surgery specimen)

• Capability to give written informed consent

• Nodal positive patients will be accepted to the registry up to 25% of the genomic low/ultralow-risk population (n=441).

Exclusion Criteria:

Patients will not be eligible for the registry for any of the following reasons:

• Any other genomic testing, besides MammaPrint®, has been performed on the tumor material

• Medical or psychological conditions that would not permit the patient to sign informed consent

• Legal incapacity or limited legal capacity

• Current participation in any interventional clinical trial which tests anticancer drugs, immunotherapeutics, or antibody treatment for any type of neoplasm

• Non-compliance of the patient

Related Conditions & MeSH terms

• Breast Neoplasms
• Female Breast Cancer

Locations

Country	Name	City	State
Germany	Marienhospital Aachen	Aachen	NRW
Germany	Klinikum St. Marien Amberg	Amberg	Bayern
Germany	DRK Kliniken Berlin Köpenick	Berlin
Germany	Medionko - Praxisklinik Krebsheilkunde Frauen	Berlin
Germany	Gynäkologisches Zentrum	Bonn	NRW
Germany	Universitätsklinikum Bonn Frauenheilkunde	Bonn	NRW
Germany	Marienhospital, Klinik für Gynäkologie und Geburtshilfe	Bottrop
Germany	DIAKO Ev. Diakonie-Krankenhaus gemeinnützige GmbH	Bremen
Germany	St. Vincenz-Krankenhaus Datteln	Datteln	NRW
Germany	Luisenkrankenhaus GmbH Co KG	Düsseldorf	NRW
Germany	Marien Hospital Düsseldorf	Düsseldorf	NRW
Germany	AGAPLESION Diakonie Hamburg	Hamburg
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Gynäkologische Praxisklinik Hamburg-Harburg	Hamburg
Germany	Klinikum Hanau GmbH	Hanau	Hessen
Germany	ViDia Christliche Kliniken Karlsruhe	Karlsruhe	Baden-Wüttemberg
Germany	Kliniken der Stadt Köln	Köln	NRW
Germany	Helios Klinikum Krefeld, Zentrum für Ambulante Gynäkologische Onkologie - Studienabteilung	Krefeld
Germany	Brustzentrum Niederrhein, Johanniter Bethesda Krankenhaus	Moenchengladbach	NRW
Germany	Klinikum der Universität München	München	Bayern
Germany	Med. Zentrum f. Hämatologie und Onkologie München	München	Bayern
Germany	Studienzentrum Onkologie Ravensburg	Ravensburg	Baden-Wüttemberg
Germany	Mathias-Spital-Rheine	Rheine	NRW
Germany	Klinikum Südstadt	Rostock	Mecklenburg-Vorpommern
Germany	MKS St. Paulus Schwerte (ehemals Marienkrankenhaus)	Schwerte
Germany	Klinikum Traunstein, Frauenklinik Südostbayern	Traunstein
Germany	Praxisnetzwerk Hämatologie/int. Onkologie	Troisdorf	NRW
Germany	Christliches Klinikum Unna gGmbH	Unna	NRW
Germany	Evangelisches Krankenhaus Wesel GmbH	Wesel	NRW
Germany	St. Josefs-Hospital Wiesbaden GmbH	Wiesbaden	Hessen
Germany	Klinikum Worms	Worms	Rheinland-Pfalz
Germany	Helios Klinikum Wuppertal	Wuppertal	NRW

Sponsors (2)

Lead Sponsor	Collaborator
West German Study Group	Agendia

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-year distant recurrence-free interval (dRFI, according to STEEP criteria version 2.0)	dRFIin all patients treated by (intensified) endocrine therapy alone (and with ovarian suppression in cases with enhanced clinical risk according to current AGO-recommendations)	5 years
Secondary	10-year dRFI	dRFI, according to STEEP criteria 2.0, in all patients treated by (intensified) endocrine therapy alone (with ovarian suppression in cases with higher clinical risk)	10 years
Secondary	5-year dRFI	dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS	5 years
Secondary	10-year dRFI	dRFI, according to STEEP criteria 2.0,in all patients treated by SOC chemotherapy treatment followed by ET+/-OFS	10 years
Secondary	5-year dDFS	distant disease-free survival (dDFS, according to STEEP 2.0) in all patients and all treatment groups (i.e., patients treated by ET alone, ET + GnRH, chemotherapy followed by ET, chemotherapy followed by ET + GnRH, OFS-treated patients)	5 years
Secondary	10-year dDFS	distant disease-free survival (dDFS, according to STEEP 2.0) in all patients and all treatment groups (i.e., patients treated by ET alone, ET + GnRH, chemotherapy followed by ET, chemotherapy followed by ET + GnRH, OFS-treated patients)treatment followed by ET+/-OFS	10 years
Secondary	5-year OS	overall survival (OS) in all patients and all treatment groups	5 years
Secondary	10-year OS	overall survival (OS) in all patients and all treatment groups	10 years
Secondary	5-year breast cancer-free interval (BCFI, according to STEEP 2.0)	BCFI in all patients and all treatment groups	5 years
Secondary	10-year breast cancer-free interval (BCFI, according to STEEP 2.0)	BCFI in all patients and all treatment groups	10 years
Secondary	EORTC quality of life questionnaire BR23	compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.	every 3 months within 1st year
Secondary	EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	every 3 months within 1st year
Secondary	EORTC quality of life questionnaire BR23	compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.	every 6 months within 2nd year
Secondary	EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	every 6 months within 2nd year
Secondary	EORTC quality of life questionnaire BR23	compare the course of Qol between baseline and further defined timepoints; 23 items, symptom scales/items and functional scales/items, all of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.	yearly until 5 years
Secondary	EORTC quality of life questionnaire C30	compare the course of Qol between baseline and further defined timepoints; 30 items, 10 subscales, the higher the rating, the worse.	yearly until 5 years
Secondary	adherence to OFS and endocrine treatment	Duration of intake of OFS and endocrine treatment in all patients	10 years
Secondary	concordance between BluePrint®/MammaPrint® molecular subtyping results vs. pathological immune-histochemistry results	concordance between BluePrint®/MammaPrint® molecular subtyping results and pathological immune-histochemistry results with respect to tumour type	10 years
Secondary	endocrine response measured by post-endocrine Ki-67	post-endocrine Ki-67 (=10% and/or relative change vs. baseline) in patients treated by preoperative ET	10 years
Secondary	5-year iDFS in node-negative patients with ultralow MammaPrint	node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)	5 years
Secondary	10-year iDFS in node-negative patients with ultralow MammaPrint	node-negative patients with ultralow MammaPrint® treated by shorter duration of ET (2-3 years at investigator decision)	10 years