Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04675827




Registration number
NCT04675827
Ethics application status
Date submitted
25/11/2020
Date registered
19/12/2020
Date last updated
5/09/2023

Titles & IDs
Public title
De-escalation Adjuvant Chemo in HER2+/ER-/Node-neg Early BC Patients Who Achieved pCR After Neoadjuvant Chemo & Dual HER2 Blockade
Scientific 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
Secondary ID [1] 0 0
IJB-EBC-Decrescendo-2020
Universal Trial Number (UTN)
Trial acronym
Decrescendo
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-positive Breast Cancer 0 0
ER-Negative Breast Cancer 0 0
PR-Negative Breast Cancer 0 0
Node-negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pertuzumab and tratuzumab fixed dose combination
Treatment: Drugs - Trastuzumab emtansine

Experimental: RCB = 0 - 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.

Experimental: RCB > 0 - 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.


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

Treatment: Drugs: Trastuzumab emtansine
Treatment administration: adjuvant T-DM1 for 14 cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
3-year RFS in HER2-enriched subjects who achieve a pCR
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
3-year RFS in all subjects who achieve a pCR.
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
5-year RFS in all subjects who achieve a pCR.
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
pCR (in the overall population)
Timepoint [3] 0 0
during procedure
Secondary outcome [4] 0 0
3-year RFS (survival rates)
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
3-year invasive disease-free survival (iDFS) (survival rates)
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
3-year distant disease-free survival (dDFS) (survival rates)
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
3-year overall survival (OS) (survival rates)
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Recurrence-free interval (RFI) (Time)
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
5-year RFS (survival rates)
Timepoint [9] 0 0
5 years
Secondary outcome [10] 0 0
5-year invasive disease-free survival (iDFS) (survival rates)
Timepoint [10] 0 0
5 years
Secondary outcome [11] 0 0
5-year distant disease-free survival (dDFS) (survival rates)
Timepoint [11] 0 0
5 years
Secondary outcome [12] 0 0
5-year overall survival (OS)(survival rates)
Timepoint [12] 0 0
5 years
Secondary outcome [13] 0 0
Recurrence-free interval (RFI) (time)
Timepoint [13] 0 0
5 years
Secondary outcome [14] 0 0
Number of participants experiencing an Adverse Event
Timepoint [14] 0 0
study treatment plus follow-up of 30 days ( Time Frame: Up to approximately 17 months )
Secondary outcome [15] 0 0
Number of participants experiencing an Serious Adverse Event
Timepoint [15] 0 0
through study completion estimated 60 months

Eligibility
Key inclusion criteria
1. Male or female.
2. Age =18 years old.
3. Eastern Cooperative Oncology Group (ECOG) performance status =1.
4. 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]).
5. Must have histologically confirmed diagnosis of HER2-positive and ER-negative/PR-negative breast cancer (analysis performed by the local laboratory).

1. 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).
2. 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.
6. 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.
7. 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.
8. Serum pregnancy test (for women of childbearing potential) negative within 7 days prior to treatment start.
9. 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.
10. 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
11. 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
12. Adequate renal function as defined below:

• Creatinine =1.5 x UNL or creatinine clearance >60 mL/min/1.73 m2
13. Completion of all necessary screening procedures within 28 days prior to enrolment.
14. Adequate cardiac function, defined as a left ventricular ejection fraction =55% estimated by echocardiogram (ECHO) or multiple-gated acquisition scintigraphy (MUGA).
15. 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.
16. Signed Informed Consent form (ICF) obtained prior to any study related procedure.
17. Subject is willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.

Inclusion criterion applicable to FRANCE only:
18. Affiliated to the French Social Security System.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant and/or lactating women.
2. Bilateral invasive breast cancer.
3. 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).
4. 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.
5. Previous exposure to any anti-HER2 treatment.
6. Concomitant exposure to any investigational products as part of a clinical trial within 30 days prior to enrolment.
7. 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.
8. 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.
9. 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)
10. 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.
11. Peripheral neuropathy (CTCAE version 5) grade =2.
12. Major surgery within 14 days prior to enrolment.
13. 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).
14. Previous allogeneic bone marrow transplant.
15. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE grade =3).
16. Subjects who received live attenuated vaccines within 14 days before enrolment.

Exclusion criterion applicable to FRANCE only:
17. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Suspended
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2029
Actual
Sample size
Target
1065
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Icon Cancer Centre Wesley - Auchenflower
Recruitment hospital [2] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [3] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [4] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [5] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [7] 0 0
Monash Medical Centre (Clayton) - Clayton
Recruitment hospital [8] 0 0
Coffs Harbour Health Campus - Coffs Harbour
Recruitment hospital [9] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [10] 0 0
Townsville University Hospital - Douglas
Recruitment hospital [11] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [12] 0 0
Gosford Hospital - Gosford
Recruitment hospital [13] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [14] 0 0
Icon Cancer Centre Hobart - Hobart
Recruitment hospital [15] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [16] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [17] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [18] 0 0
Macquarie University - North Ryde
Recruitment hospital [19] 0 0
Mater Hospital - North Sydney
Recruitment hospital [20] 0 0
Sunshine Hospital - Saint Albans
Recruitment hospital [21] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [22] 0 0
Westmead Hospital - Westmead
Recruitment hospital [23] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Auchenflower
Recruitment postcode(s) [2] 0 0
- Ballarat
Recruitment postcode(s) [3] 0 0
- Bendigo
Recruitment postcode(s) [4] 0 0
- Birtinya
Recruitment postcode(s) [5] 0 0
- Box Hill
Recruitment postcode(s) [6] 0 0
- Camperdown
Recruitment postcode(s) [7] 0 0
- Clayton
Recruitment postcode(s) [8] 0 0
- Coffs Harbour
Recruitment postcode(s) [9] 0 0
- Concord
Recruitment postcode(s) [10] 0 0
- Douglas
Recruitment postcode(s) [11] 0 0
- Gateshead
Recruitment postcode(s) [12] 0 0
- Gosford
Recruitment postcode(s) [13] 0 0
- Herston
Recruitment postcode(s) [14] 0 0
- Hobart
Recruitment postcode(s) [15] 0 0
- Liverpool
Recruitment postcode(s) [16] 0 0
- Melbourne
Recruitment postcode(s) [17] 0 0
- Nedlands
Recruitment postcode(s) [18] 0 0
- North Ryde
Recruitment postcode(s) [19] 0 0
- North Sydney
Recruitment postcode(s) [20] 0 0
- Saint Albans
Recruitment postcode(s) [21] 0 0
- Waratah
Recruitment postcode(s) [22] 0 0
- Westmead
Recruitment postcode(s) [23] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Wilrijk
Country [2] 0 0
Belgium
State/province [2] 0 0
Aalst
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerp
Country [4] 0 0
Belgium
State/province [4] 0 0
Brasschaat
Country [5] 0 0
Belgium
State/province [5] 0 0
Brussels
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles
Country [7] 0 0
Belgium
State/province [7] 0 0
Charleroi
Country [8] 0 0
Belgium
State/province [8] 0 0
Lier
Country [9] 0 0
Belgium
State/province [9] 0 0
Liège
Country [10] 0 0
Belgium
State/province [10] 0 0
Namur
Country [11] 0 0
France
State/province [11] 0 0
Angers
Country [12] 0 0
France
State/province [12] 0 0
Avignon
Country [13] 0 0
France
State/province [13] 0 0
Bayonne
Country [14] 0 0
France
State/province [14] 0 0
Besançon
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux
Country [16] 0 0
France
State/province [16] 0 0
Brest
Country [17] 0 0
France
State/province [17] 0 0
Caen
Country [18] 0 0
France
State/province [18] 0 0
Clermont-Ferrand
Country [19] 0 0
France
State/province [19] 0 0
Dijon
Country [20] 0 0
France
State/province [20] 0 0
Grenoble
Country [21] 0 0
France
State/province [21] 0 0
Lille
Country [22] 0 0
France
State/province [22] 0 0
Limoges
Country [23] 0 0
France
State/province [23] 0 0
Lorient
Country [24] 0 0
France
State/province [24] 0 0
Lyon
Country [25] 0 0
France
State/province [25] 0 0
Marseille
Country [26] 0 0
France
State/province [26] 0 0
Metz-Tessy
Country [27] 0 0
France
State/province [27] 0 0
Montpellier
Country [28] 0 0
France
State/province [28] 0 0
Nantes
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Perpignan
Country [31] 0 0
France
State/province [31] 0 0
Pierre-Bénite
Country [32] 0 0
France
State/province [32] 0 0
Poitiers
Country [33] 0 0
France
State/province [33] 0 0
Reims
Country [34] 0 0
France
State/province [34] 0 0
Rouen
Country [35] 0 0
France
State/province [35] 0 0
Saint-Cloud
Country [36] 0 0
France
State/province [36] 0 0
Strasbourg
Country [37] 0 0
France
State/province [37] 0 0
Toulouse
Country [38] 0 0
France
State/province [38] 0 0
Villejuif
Country [39] 0 0
Israel
State/province [39] 0 0
Ramat Gan
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Cheonan
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Daegu
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Goyang-si
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Incheon
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seongnam-si
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Seongnam
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Seoul
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Suwon si
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Ulsan
Country [49] 0 0
Switzerland
State/province [49] 0 0
Aarau
Country [50] 0 0
Switzerland
State/province [50] 0 0
Baden
Country [51] 0 0
Switzerland
State/province [51] 0 0
Basel
Country [52] 0 0
Switzerland
State/province [52] 0 0
Frauenfeld
Country [53] 0 0
Switzerland
State/province [53] 0 0
Fribourg
Country [54] 0 0
Switzerland
State/province [54] 0 0
Winterthur

Funding & Sponsors
Primary sponsor type
Other
Name
Jules Bordet Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Breast International Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Hoffmann-La Roche
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
International Drug Development Institute
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Institut Curie
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Martine Piccart, PD, PhD
Address 0 0
Jules Bordet Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04675827