De-escalation Adjuvant Chemo in HER2+/ER-/node-neg Early BC Patients Who Achieved PCR After Neoadjuvant Chemo & Dual HER2 Blockade

NCT04675827 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: IJB-EBC-Decrescendo-2020
• Study Type: interventional
• Target: 139
• Locations: 6 countries
• Sites: 85

Brief 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 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).

Conditions

HER2-positive Breast Cancer; ER-Negative Breast Cancer; PR-Negative Breast Cancer; Node-negative Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (15)

• 3-year RFS in all subjects who achieve a pCR.

  3 years

• 5-year RFS in all subjects who achieve a pCR.

  5 years

• pCR (in the overall population)

  during procedure

• 3-year RFS (survival rates)

  3 years

• 3-year invasive disease-free survival (iDFS) (survival rates)

  3 years

Study Arms (2)

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.

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.

Drug: Trastuzumab emtansine

Interventions

Pertuzumab and tratuzumab fixed dose combination DRUG

Treatment administration: adjuvant pertuzumab and trastuzumab fixed dose combination SC for 14 cycles

Also known as: Adjuvant pertuzumab + trastuzumab FDC SC for 14 cycles, Fixed-dose combination of Perjeta and Herceptin for subcutaneous injection for 14 cycles

RCB = 0

Trastuzumab emtansine DRUG

Treatment administration: adjuvant T-DM1 for 14 cycles.

Also known as: Adjuvant T-DM1

RCB > 0

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Breast International Group: collaborator
• Hoffmann-La Roche: collaborator
• International Drug Development Institute: collaborator
• Institut Curie: collaborator

Study Sites (85)

Icon Cancer Centre Wesley

Auchenflower, Australia

Location

Ballarat Health Services

Ballarat, Australia

Location

Bendigo Hospital

Bendigo, Australia

Location

Sunshine Coast University Hospital

Birtinya, Australia

Location

Box Hill Hospital

Box Hill, Australia

Location

Chris O'Brien Lifehouse

Camperdown, Australia

Location

Monash Medical Centre (Clayton)

Clayton, Australia

Location

Coffs Harbour Health Campus

Coffs Harbour, Australia

Location

Concord Repatriation General Hospital

Concord, Australia

Location

Townsville University Hospital

Douglas, Australia

Location

Lake Macquarie Private Hospital

Gateshead, Australia

Location

Gosford Hospital

Gosford, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Australia

Location

Icon Cancer Centre Hobart

Hobart, Australia

Location

Liverpool Hospital

Liverpool, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Australia

Location

Macquarie University

North Ryde, Australia

Location

Mater Hospital

North Sydney, Australia

Location

Sunshine Hospital

Saint Albans, Australia

Location

Calvary Mater Newcastle

Waratah, Australia

Location

Westmead Hospital

Westmead, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Australia

Location

GZA Ziekenhuisen Campus Sint-Augustinus - Iridium Kankernetwerk

Antwerp, Wilrijk, Belgium

Location

OLV ziekenhuis

Aalst, Belgium

Location

Cliniques Universtaires Saint-Luc

Brussels, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, Belgium

Location

Heilig Hartziekenhuis

Lier, Belgium

Location

Centre Hospitalier Chretien MontLegia

Liège, Belgium

Location

CHU UCL Namur Sainte-Elisabeth

Namur, Belgium

Location

Institut de Cancérologie de l'Ouest - Angers

Angers, France

Location

Institut Sainte Catherine

Avignon, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, France

Location

CHRU Jean Minjoz

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Location

CHU Morvan

Brest, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Hopital Michallon

Grenoble, France

Location

Centre Oscar Lambret

Lille, France

Location

CHU de Limoges

Limoges, France

Location

GHBS Lorient

Lorient, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

CH Annecy Genevois

Metz-Tessy, France

Location

Centre de Cancerologie du Grand Montpellier

Montpellier, France

Location

Hopital privé du Confluent

Nantes, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, France

Location

Hopital Tenon

Paris, France

Location

Institut Curie - Paris

Paris, France

Location

CH Perpignan

Perpignan, France

Location

Hopital Lyon Sud

Pierre-Bénite, France

Location

CHU Poitiers

Poitiers, France

Location

Institut Godinot

Reims, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie - Saint-Cloud

Saint-Cloud, France

Location

Clinique Saint Anne

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Soon Chun Hyang University Cheonan Hospital

Cheonan, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Inha University Hospital

Incheon, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

CHA bundang Medical Center

Seongnam-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Ewha Womans University Mokdong Hospital

Seoul, South Korea

Location

Korea university anam hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul ST. Mary's Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Ulsan University Hospital

Ulsan, South Korea

Location

Hirslanden Klinik - Tumor Zentrum

Aarau, Switzerland

Location

Kantonsspital Baden

Baden, Switzerland

Location

Universitatsspital Basel

Basel, Switzerland

Location

Kantonsspital Frauenfeld/Frauenklinik

Frauenfeld, Switzerland

Location

Hopital Daler - Centre du Sein

Fribourg, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Switzerland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Injections, Subcutaneous; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Martine Piccart, PD, PhD

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 19, 2020
• Study Start: January 17, 2022
• Primary Completion: November 26, 2024
• Study Completion: November 26, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-04

Locations

CH (6); BE (8); AU (23); IL (1); FR (31); KR (16)