HER2-positive Breast CancerPhase 2DecrescendoNCT04675827
De-escalation Adjuvant Chemo in HER2+/ER-/node-neg Early BC Patients Who Achieved PCR After Neoadjuvant Chemo & Dual HER2 Blockade
A Phase 2 study testing Pertuzumab and tratuzumab fixed dose combination and Trastuzumab emtansine in people with HER2-positive Breast Cancer and ER-Negative Breast Cancer, run by Jules Bordet Institute at 85 sites in 6 countries.
Trial summary
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly IV paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, ER-Negative Breast Cancer, PR-Negative Breast Cancer
- What is being tested?
- Pertuzumab and tratuzumab fixed dose combination and Trastuzumab emtansine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 85 sitesin 6 countries
- Study dates
- 17 Jan 2022to 26 Nov 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female.
- Age ≥18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
- Subjects whose tumour measures ≥15 mm and ≤50 mm, according to clinical staging performed with imaging exams (either mammography, ultrasound or breast magnetic resonance imaging [MRI]).
- Must have histologically confirmed diagnosis of HER2-positive and ER-negative/PR-negative breast cancer (analysis performed by the local laboratory).
- HER2-positive defined as a score of 3+ in IHC or a positive ISH (ratio of HER2 copy number/chromosome 17 ≥2 or average HER2 copy number ≥6 signals per cell).
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- ER-negative/PR-negative defined as estrogen receptor and progesterone receptor nuclear staining <1% by IHC.
- Note: patients with micro-invasive carcinoma or ductal carcinoma in situ (DCIS) without invasive disease are not eligible.
- Subjects with multifocal or multicentric invasive disease are eligible as long as all the biopsiable lesions can be characterised and are confirmed to be HER2-positive and ER and PR negative.
- Note: In the case of multifocal or multicentric disease, only the biopsy from the largest lesion should be provided.
- Node-negative disease (N0): no axillary lymph nodes identifiable at ultrasound, or in case of suspect axillary lymph nodes are identified, fine-needle aspiration or core biopsy must be carried out to confirm that axillary status is negative. Axillary micrometastases (i.e., if the greatest diameter of the nodal metastasis in a sentinel node is 0.2 mm or less) are not allowed.
- Serum pregnancy test (for women of childbearing potential) negative within 7 days prior to treatment start.
- Women of childbearing potential must agree to use 1 highly effective non-hormonal contraceptive method with a failure rate of less than 1% per year from the signing of the ICF until at least 7 months after last dose of study drugs; or they must totally abstain from any form of sexual intercourse. Men with a partner of childbearing potential must agree to use condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, during the course of this study and for at least 7 months after the last administration of study treatment.
- Adequate bone marrow and coagulation functions as defined below:
- Absolute neutrophil count ≥1500 /µL or 1.5x109/L
- Haemoglobin ≥9 g/dL (blood transfusions to reach these levels of haemoglobin are allowed)
- Platelets ≥100,000/µL or 100x109/L
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 ×ULN
- Adequate liver function as defined below:
- Serum total bilirubin ≤1.5 x ULN. In case of known Gilbert's syndrome ≤3xUNL is allowed
- AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
- Alkaline phosphatase ≤2.5 x ULN
- Adequate renal function as defined below:
- Creatinine ≤1.5 x UNL or creatinine clearance >60 mL/min/1.73 m2
- Completion of all necessary screening procedures within 28 days prior to enrolment.
- Adequate cardiac function, defined as a left ventricular ejection fraction ≥55% estimated by echocardiogram (ECHO) or multiple-gated acquisition scintigraphy (MUGA).
- Availability of a pre-treatment tumour biopsy sample as specified below:
- At least one FFPE tumour block must be available for central evaluation. Whenever possible, two FFPE tumour blocks should be available (preferred).
- If a block cannot be provided, 25 unstained FFPE slides of 4 µm thickness from the pre-treatment tumour biopsy must be provided as an alternative. These slides must be freshly cut prior the shipment to the sponsor.
- In either case, the local pathologist must evaluate an H\&E stained slide to ensure that the tumour surface is at least 4 mm² and that tumour cellularity is ≥10%.
- Note 1: Tumour biopsy must be sent to the central research laboratory as soon as the patient is confirmed by the local investigator to be eligible for the study.
- Note 2: the inclusion of the subject is only based on local assessments. A central review of HER2, ER, and PR status will be performed at posteriori for quality control purposes.
- Signed Informed Consent form (ICF) obtained prior to any study related procedure.
- Subject is willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.
- Affiliated to the French Social Security System.
Who cannot join
- Pregnant and/or lactating women.
- Bilateral invasive breast cancer.
- Evidence of metastatic breast cancer: all subjects must have had a CT/MRI scan of the thorax/abdomen/pelvis to rule out metastatic breast cancer prior to enrolment. FDG/PET-CT can be used as an alternative to replace all the exams above. A screening bone scan must have been done if ALP and/or corrected calcium levels were above the institutional upper limits at screening (if PET/CT was used as an alternative imaging exam, a bone scan and/or CT/MRI is not required).
- Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator's opinion, may interfere with completion of the study.
- Previous exposure to any anti-HER2 treatment.
- Concomitant exposure to any investigational products as part of a clinical trial within 30 days prior to enrolment.
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- Subject with second primary malignancies diagnosed ≤ 5 years before enrolment in the study. Exceptions are: adequately treated non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ of the breast, and any other solid or haematological tumour diagnosed > 5 years before enrolment and for which no chemotherapy and no systemic treatment were necessary, with no evidence of disease recurrence.
- Resting electrocardiogram (ECG) with QTc >470 msec detected on at 2 or more time points within a 24-hour period, or family history of long QT syndrome.
- Serious cardiac illness or medical conditions including, but not confined to, the following:
- History of NCI CTCAE (v4) Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II
- High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate = or > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block) - Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality
- Angina pectoris requiring anti-anginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Evidence of myocardial infarction within 12 months prior to randomization
- Poorly controlled hypertension (i.e., systolic > 180 mm Hg or diastolic > 100 mmHg)
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
- Peripheral neuropathy (CTCAE version 5) grade ≥2.
- Major surgery within 14 days prior to enrolment.
- Subject with HIV, Hepatitis B or Hepatitis C infection documented by serology, except for those subjects with a previous exposure to Hepatitis B who developed an effective immune response (HBSAg-negative and anti-HBS-positive).
- Previous allogeneic bone marrow transplant.
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE grade ≥3).
- Subjects who received live attenuated vaccines within 14 days before enrolment.
- Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.
Trial locations and contacts
85 sites in 6 countries.
85 sites in 6 countries
France31 sites
Institut de Cancérologie de l'Ouest - Angers
Angers
Institut Sainte Catherine
Avignon
Centre Hospitalier de la Côte Basque
Bayonne
CHRU Jean Minjoz
Besançon
Institut Bergonié
Bordeaux
Polyclinique Bordeaux Nord Aquitaine
Bordeaux
CHU Morvan
Brest
Centre François Baclesse
Caen
Centre Jean Perrin
Clermont-Ferrand
Centre Georges François Leclerc
Dijon
Hopital Michallon
Grenoble
Centre Oscar Lambret
Lille
CHU de Limoges
Limoges
GHBS Lorient
Lorient
Centre Léon Bérard
Lyon
Institut Paoli Calmettes
Marseille
CH Annecy Genevois
Metz-Tessy
Centre de Cancerologie du Grand Montpellier
Montpellier
Hopital privé du Confluent
Nantes
Groupe Hospitalier Diaconesses Croix Saint-Simon
Paris
Hopital Tenon
Paris
Institut Curie - Paris
Paris
CH Perpignan
Perpignan
Hopital Lyon Sud
Pierre-Bénite
CHU Poitiers
Poitiers
Institut Godinot
Reims
Centre Henri Becquerel
Rouen
Institut Curie - Saint-Cloud
Saint-Cloud
Clinique Saint Anne
Strasbourg
Institut Claudius Regaud
Toulouse
Institut Gustave Roussy
Villejuif
Australia23 sites
Icon Cancer Centre Wesley
Auchenflower
Ballarat Health Services
Ballarat
Bendigo Hospital
Bendigo
Sunshine Coast University Hospital
Birtinya
Box Hill Hospital
Box Hill
Chris O'Brien Lifehouse
Camperdown
Monash Medical Centre (Clayton)
Clayton
Coffs Harbour Health Campus
Coffs Harbour
Concord Repatriation General Hospital
Concord
Townsville University Hospital
Douglas
Lake Macquarie Private Hospital
Gateshead
Gosford Hospital
Gosford
Royal Brisbane and Women's Hospital
Herston
Icon Cancer Centre Hobart
Hobart
Liverpool Hospital
Liverpool
Peter MacCallum Cancer Centre
Melbourne
Sir Charles Gairdner Hospital
Nedlands
Macquarie University
North Ryde
Mater Hospital
North Sydney
Sunshine Hospital
Saint Albans
Calvary Mater Newcastle
Waratah
Westmead Hospital
Westmead
Princess Alexandra Hospital
Woolloongabba
South Korea16 sites
Soon Chun Hyang University Cheonan Hospital
Cheonan
Keimyung University Dongsan Hospital
Daegu
National Cancer Center
Goyang-si
Gachon University Gil Medical Center
Incheon
Inha University Hospital
Incheon
Seoul National University Bundang Hospital
Seongnam
CHA bundang Medical Center
Seongnam-si
Asan Medical Center
Seoul
Ewha Womans University Mokdong Hospital
Seoul
Korea university anam hospital
Seoul
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Seoul ST. Mary's Hospital
Seoul
Severance Hospital
Seoul
Ajou University Hospital
Suwon
Ulsan University Hospital
Ulsan
Belgium8 sites
OLV ziekenhuis
Aalst
GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk
Antwerp, Wilrijk
Cliniques Universtaires Saint-Luc
Brussels
Institut Jules Bordet
Brussels
Grand Hôpital de Charleroi
Charleroi
Centre Hospitalier Chretien MontLegia
Liège
Heilig Hartziekenhuis
Lier
CHU UCL Namur Sainte-Elisabeth
Namur
Switzerland6 sites
Hirslanden Klinik - Tumor Zentrum
Aarau
Kantonsspital Baden
Baden
Universitatsspital Basel
Basel
Kantonsspital Frauenfeld/Frauenklinik
Frauenfeld
Hopital Daler - Centre du Sein
Fribourg
Kantonsspital Winterthur
Winterthur
About this study
Official title: De-Escalation of Adjuvant Chemotherapy in HER2-positive, Estrogen Receptor-negative, Node-negative Early Breast Cancer Patients Who Achieved Pathological Complete Response After Neoadjuvant Chemotherapy and Dual HER2 Blockade
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly IV paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
Read more
After surgery, subjects who achieve a pCR (defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Read the detailed description
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly intravenous (IV) paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pathologic complete response (pCR, defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Patients' tumour intrinsic subtype will be determined based on analysis of the PAM50 gene signature. The PAM50 gene signature, which measures the expression of 50 genes to classify tumours into 1 of 4 intrinsic subtypes (luminal A, luminal B, HER2-enriched, and basal-like), will be assessed in formalin-fixed paraffin embedded (FFPE) samples obtained at baseline. While a tumour biopsy sample must be available prior to enrolment, the PAM50 results will be generated centrally post enrolment and subsequently used to assess the primary endpoint of the study, which is the 3-year recurrence-free survival (RFS) rate in the subpopulation of subjects with HER2-enriched tumours who achieve a pCR after the neoadjuvant phase of the study.
Sub-study:
The flexible care sub-study is an open-label, randomised phase II study to be conducted in selected sites from some of the countries that participate in DECRESCENDO. After completion of neoadjuvant treatment and surgery in the main study, 121 of the subjects who achieved a pCR and thus are assigned to continue treatment with pertuzumab and trastuzumab FDC SC will be randomised at a 1:1 ratio to receive 3 cycles of pertuzumab and trastuzumab FDC SC every 3 weeks in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period.
- Conditions
- HER2-positive Breast Cancer, ER-Negative Breast Cancer, PR-Negative Breast Cancer, Node-negative Breast Cancer
- Being tested
- Pertuzumab and tratuzumab fixed dose combination, Trastuzumab emtansine
- Keywords
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pertuzumab and tratuzumab fixed dose combinationDrug
Also called Adjuvant pertuzumab + trastuzumab FDC SC for 14 cycles, Fixed-dose combination of Perjeta and Herceptin for subcutaneous injection for 14 cycles
Treatment administration: adjuvant pertuzumab and trastuzumab fixed dose combination SC for 14 cycles
Trastuzumab emtansineDrug
Also called Adjuvant T-DM1
Treatment administration: adjuvant T-DM1 for 14 cycles.
| Study group | Role | What they receive |
|---|---|---|
| RCB = 0 | Experimental | Treatment administration: adjuvant pertuzumab + trastuzumab (P+T) fixed dose combination (FDC) SC for 14 cycles.
Sub-study: 121 of the subjects who achieved a pCR (thus assigned to continue treatment with P+T FDC SC) will be randomised at a 1:1 ratio to receive 3 cycles of P+T FDC SC in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period. Receives: Drug: Pertuzumab and tratuzumab fixed dose combination |
| RCB > 0 | Experimental | Treatment administration:adjuvant T-DM1 for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1. Receives: Drug: Trastuzumab emtansine |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year RFS in HER2-enriched subjects who achieve a pCR
3-year RFS, defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause; in subjects with HER2-enriched, ER-negative/PR-negative, clinically node-negative breast cancers who achieve a pCR after neoadjuvant treatment.
Measured: 3 years
Secondary outcomes (15)
3-year RFS in all subjects who achieve a pCR.
3-year RFS in all subjects who achieve a pCR.
Measured: 3 years
5-year RFS in all subjects who achieve a pCR.
5-year RFS in all subjects who achieve a pCR.
Measured: 5 years
pCR (in the overall population)
To assess pCR rates in the overall population and by primary tumour dimension. pCR (in the overall population) is defined as the absence of residual invasive tumour in the breast and axillary lymph nodes (pT0/Tis pN0) at surgery as per the local anatomo-pathological report.
Measured: during procedure
3-year RFS (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 3-year RFS The RFS is defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause
Measured: 3 years
3-year invasive disease-free survival (iDFS) (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 3-year invasive disease-free survival (iDFS) The iDFS is defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause, invasive contralateral breast cancer, second primary invasive cancer (non-breast)
Measured: 3 years
3-year distant disease-free survival (dDFS) (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
urvival rates: - 3-year distant disease-free survival (dDFS) The dDFS defined as the time from enrolment until the first occurrence of one of the following events: distant recurrence; death from breast cancer; death from non-breast cancer cause; death from unknown cause; second primary invasive cancer (non-breast);
Measured: 3 years
3-year overall survival (OS) (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 3-year overall survival (OS) The OS defined as the time from enrolment until the first occurrence of one of the following events: death from breast cancer, death from non-breast cancer cause, death from unknown cause
Measured: 3 years
Recurrence-free interval (RFI) (Time)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Time: Recurrence-free interval (RFI) The RFI is defined as the time interval between enrolment and the occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence; death from breast cancer
Measured: 3 years
5-year RFS (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 5-year RFS The RFS is defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause
Measured: 5 years
5-year invasive disease-free survival (iDFS) (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 5-year invasive disease-free survival (iDFS) The iDFS is defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause, invasive contralateral breast cancer, second primary invasive cancer (non-breast)
Measured: 5 years
5-year distant disease-free survival (dDFS) (survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 5-year distant disease-free survival (dDFS) The dDFS defined as the time from enrolment until the first occurrence of one of the following events: distant recurrence; death from breast cancer; death from non-breast cancer cause; death from unknown cause; second primary invasive cancer (non-breast);
Measured: 5 years
5-year overall survival (OS)(survival rates)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Survival rates: - 5-year overall survival (OS) The OS defined as the time from enrolment until the first occurrence of one of the following events: death from breast cancer, death from non-breast cancer cause, death from unknown cause
Measured: 5 years
Recurrence-free interval (RFI) (time)
In all population, the sub-group analysis according to the pathological response (pCR versus residual disease) and stratified by tumour size (T1 versus T2) for following outcomes:
Time: Recurrence-free interval (RFI) The RFS is defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause
Measured: 5 years
Number of participants experiencing an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation subject receiving/undergoing the study treatments (paclitaxel (or docetaxel), pertuzumab and trastuzumab FDC SC, T-DM1, surgery, radiotherapy) and which does not necessarily have a causal relationship with these study treatments. The number of participants who experience an AE (including 1 month of safety follow up) will be presented. The intensity of all AEs will be graded according to the CTCAE version 5 on a five-point scale (Grade 1 to 5).
Measured: study treatment plus follow-up of 30 days ( Time Frame: Up to approximately 17 months )
Number of participants experiencing an Serious Adverse Event
A serious adverse event (SAE) is any untoward medical occurrence that results in any of the following outcomes: Death; Life-threatening; Subject hospitalisation or prolongation of existing hospitalisation; Persistent or significant disability/incapacity; Congenital anomaly/birth defect. The number of participants who experience any SAE while receiving paclitaxel (or docetaxel), pertuzumab and trastuzumab FDC SC, T-DM1, surgery, radiotherapy (including 1 months of safety follow up) with or without the relationship to IMPs will be presented. During survival follow-up, only SAE related to IMPs will be presented.
Measured: through study completion estimated 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start17 Jan 2022
- Primary completion26 Nov 2024
- Study completion26 Nov 2024
Why it stopped: Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Eligible subjects will first receive neoadjuvant treatment then surgery. After surgery, subjects who achieve a pCR (RCB score at surgery = 0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Those with residual invasive disease (RCB score at surgery ≥ 1) will receive salvage adjuvant T-DM1 for 14 cycles. In subjects with RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the administration of T-DM1.
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Bordet Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Breast International Group, Hoffmann-La Roche, International Drug Development Institute, Institut Curie
- Responsible party
- Sponsor
- Investigators
- Martine Piccart, PD, PhD, Study chair, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04675827
- Sponsor's protocol ID
- IJB-EBC-Decrescendo-2020
- Acronym
- Decrescendo
- Status last verified
- Apr 2024
- First submitted
- 25 Nov 2020
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Boman C, Tranchell C, Liu X, Eriksson Bergman L, Toli MA, Bergh J, Foukakis T, Matikas A. Prognosis After Pathologic Complete Response to Neoadjuvant Therapy in Early-Stage Breast Cancer: A Population-Based Study. J Natl Compr Canc Netw. 2025 Mar 12;23(4):e247093. doi: 10.6004/jnccn.2024.7093.
PubMed 40073831
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- De-Escalation of Adjuvant Chemotherapy in HER2-positive, Estrogen Receptor-negative, Node-negative Early Breast Cancer Patients Who Achieved Pathological Complete Response After Neoadjuvant Chemotherapy and Dual HER2 Blockade
- ClinicalTrials.gov ID
- NCT04675827
- Acronym / sponsor ID
- Decrescendo / IJB-EBC-Decrescendo-2020
- Conditions
- HER2-positive Breast Cancer, ER-Negative Breast Cancer, PR-Negative Breast Cancer, Node-negative Breast Cancer
- Keywords
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Jules Bordet InstituteUniversity, hospital or other
- Collaborators
- Breast International Group, Hoffmann-La Roche, International Drug Development Institute, Institut Curie
- Study start
- 17 Jan 2022 (actual)
- Primary completion
- 26 Nov 2024 (actual)
- Study completion
- 26 Nov 2024 (actual)
- First posted
- 19 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly IV paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pCR (defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Detailed description
DECRESCENDO is a multicentre, open-label, dual-phase single-arm phase II de-escalation study evaluating neoadjuvant treatment with 12 administrations of weekly intravenous (IV) paclitaxel 80 mg/m2 (or IV docetaxel 75 mg/m2 every 3 weeks for 4 cycles) combined with subcutaneous (SC) fixed dose combination (FDC) of pertuzumab and trastuzumab (loading dose of 1200 mg pertuzumab and 600 mg trastuzumab, followed by 600 mg pertuzumab and 600 mg trastuzumab) every 3 weeks for 4 cycles.
Surgery will be performed according to local guidelines in all subjects after neoadjuvant treatment.
After surgery, subjects who achieve a pathologic complete response (pCR, defined as pT0/Tis pN0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Subjects with residual invasive disease will receive salvage adjuvant trastuzumab emtansine (T-DM1, 3.6 mg/kg, IV every 3 weeks) for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1.
If histopathological analysis finds that the surgical specimen from a subject with residual disease is ER-positive and/or PR-positive, adjuvant endocrine therapy may be administered concomitantly with study treatment, at the investigator's discretion and according to local guidelines.
Adjuvant radiotherapy will be mandatory after breast-conserving surgery, whereas it will be performed according to local guidelines after mastectomy, and it will be administered concomitantly with pertuzumab and trastuzumab FDC SC in subjects who achieve a pCR, and concomitantly with T-DM1 in subjects with residual invasive disease (after anthracycline-based chemotherapy in subjects assigned to receive this treatment).
Patients' tumour intrinsic subtype will be determined based on analysis of the PAM50 gene signature. The PAM50 gene signature, which measures the expression of 50 genes to classify tumours into 1 of 4 intrinsic subtypes (luminal A, luminal B, HER2-enriched, and basal-like), will be assessed in formalin-fixed paraffin embedded (FFPE) samples obtained at baseline. While a tumour biopsy sample must be available prior to enrolment, the PAM50 results will be generated centrally post enrolment and subsequently used to assess the primary endpoint of the study, which is the 3-year recurrence-free survival (RFS) rate in the subpopulation of subjects with HER2-enriched tumours who achieve a pCR after the neoadjuvant phase of the study.
Sub-study:
The flexible care sub-study is an open-label, randomised phase II study to be conducted in selected sites from some of the countries that participate in DECRESCENDO. After completion of neoadjuvant treatment and surgery in the main study, 121 of the subjects who achieved a pCR and thus are assigned to continue treatment with pertuzumab and trastuzumab FDC SC will be randomised at a 1:1 ratio to receive 3 cycles of pertuzumab and trastuzumab FDC SC every 3 weeks in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Eligible subjects will first receive neoadjuvant treatment then surgery. After surgery, subjects who achieve a pCR (RCB score at surgery = 0) will receive adjuvant pertuzumab and trastuzumab FDC SC for additional 14 cycles. Those with residual invasive disease (RCB score at surgery ≥ 1) will receive salvage adjuvant T-DM1 for 14 cycles. In subjects with RCB score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the administration of T-DM1.
| Arm | Type | Receives |
|---|---|---|
| RCB = 0 | Experimental | Drug: Pertuzumab and tratuzumab fixed dose combinationTreatment administration: adjuvant pertuzumab + trastuzumab (P+T) fixed dose combination (FDC) SC for 14 cycles. Sub-study: 121 of the subjects who achieved a pCR (thus assigned to continue treatment with P+T FDC SC) will be randomised at a 1:1 ratio to receive 3 cycles of P+T FDC SC in the hospital, followed by 3 cycles in another setting outside the hospital, or to the same treatment starting with 3 cycles outside the hospital followed by 3 cycles in the hospital (treatment cross-over period). After the first 6 cycles of adjuvant treatment, subjects will be asked to choose between continuing treatment (for the remaining 8 cycles, for a total of 14 cycles) within or outside the hospital, according to their preference (treatment continuation period). Subjects can request to change from outside the hospital to in the hospital administration (and vice-versa) at any moment during the treatment continuation period, but not in the treatment cross-over period. |
| RCB > 0 | Experimental | Drug: Trastuzumab emtansineTreatment administration:adjuvant T-DM1 for 14 cycles. In subjects whose residual invasive disease is classified per Residual Cancer Burden (RCB) score as ≥2, 3 to 4 cycles of anthracycline-based chemotherapy may be administered, at the investigator's discretion, before the 14 cycles of T-DM1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Male or female.
- Age ≥18 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
- Subjects whose tumour measures ≥15 mm and ≤50 mm, according to clinical staging performed with imaging exams (either mammography, ultrasound or breast magnetic resonance imaging [MRI]).
- Must have histologically confirmed diagnosis of HER2-positive and ER-negative/PR-negative breast cancer (analysis performed by the local laboratory).
Key exclusion criteria (24 listed)
- Pregnant and/or lactating women.
- Bilateral invasive breast cancer.
- Evidence of metastatic breast cancer: all subjects must have had a CT/MRI scan of the thorax/abdomen/pelvis to rule out metastatic breast cancer prior to enrolment. FDG/PET-CT can be used as an alternative to replace all the exams above. A screening bone scan must have been done if ALP and/or corrected calcium levels were above the institutional upper limits at screening (if PET/CT was used as an alternative imaging exam, a bone scan and/or CT/MRI is not required).
- Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the investigator's opinion, may interfere with completion of the study.
- Previous exposure to any anti-HER2 treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pertuzumab and tratuzumab fixed dose combinationAlso: Adjuvant pertuzumab + trastuzumab FDC SC for 14 cycles, Fixed-dose combination of Perjeta and Herceptin for subcutaneous injection for 14 cyclesTreatment administration: adjuvant pertuzumab and trastuzumab fixed dose combination SC for 14 cycles | Drug | RCB = 0 |
| Trastuzumab emtansineAlso: Adjuvant T-DM1Treatment administration: adjuvant T-DM1 for 14 cycles. | Drug | RCB > 0 |
Primary outcome
3-year RFS in HER2-enriched subjects who achieve a pCR
Time frame: 3 years
3-year RFS, defined as the time from enrolment until the first occurrence of one of the following events: invasive ipsilateral breast tumour recurrence, local/regional invasive recurrence, distant recurrence, death from breast cancer, death attributable to any cause other than breast cancer, death from unknown cause; in subjects with HER2-enriched, ER-negative/PR-negative, clinically node-negative breast cancers who achieve a pCR after neoadjuvant treatment.
15 secondary outcomes
3-year RFS in all subjects who achieve a pCR.
Time frame: 3 years
5-year RFS in all subjects who achieve a pCR.
Time frame: 5 years
pCR (in the overall population)
Time frame: during procedure
3-year RFS (survival rates)
Time frame: 3 years
3-year invasive disease-free survival (iDFS) (survival rates)
Time frame: 3 years
3-year distant disease-free survival (dDFS) (survival rates)
Time frame: 3 years
3-year overall survival (OS) (survival rates)
Time frame: 3 years
Recurrence-free interval (RFI) (Time)
Time frame: 3 years
5-year RFS (survival rates)
Time frame: 5 years
5-year invasive disease-free survival (iDFS) (survival rates)
Time frame: 5 years
5-year distant disease-free survival (dDFS) (survival rates)
Time frame: 5 years
5-year overall survival (OS)(survival rates)
Time frame: 5 years
Recurrence-free interval (RFI) (time)
Time frame: 5 years
Number of participants experiencing an Adverse Event
Time frame: study treatment plus follow-up of 30 days ( Time Frame: Up to approximately 17 months )
Number of participants experiencing an Serious Adverse Event
Time frame: through study completion estimated 60 months
Results and safety
The study was stopped early (reason given: Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Derived from this study: PubMed 40073831Boman C, Tranchell C, Liu X, Eriksson Bergman L, Toli MA, Bergh J, Foukakis T, Matikas A. Prognosis After Pathologic Complete Response to Neoadjuvant Therapy in Early-Stage Breast Cancer: A Population-Based Study. J Natl Compr Canc Netw. 2025 Mar 12;23(4):e247093. doi: 10.6004/jnccn.2024.7093.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martine Piccart, PD, PhD study chair
Jules Bordet Institute
85 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pertuzumab and tratuzumab fixed dose combination and Trastuzumab emtansine in people with HER2-positive Breast Cancer and ER-Negative Breast Cancer, run by Jules Bordet Institute at 85 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 85 sites in France, Australia, South Korea, Belgium, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year RFS in HER2-enriched subjects who achieve a pCR (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04675827, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.