Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000011482
Ethics application status
Approved
Date submitted
17/12/2003
Date registered
17/12/2003
Date last updated
13/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
HERA (HERceptin Adjuvant) Trial
Scientific title
HERA: A randomised three-arm multi-centre comparison of 1 year and 2 years of Herceptin® versus no Herceptin® in women with HER2-positive primary breast cancer who have completed adjuvant chemotherapy.
Secondary ID [1] 36 0
National Clinical Trials Registry: NCTR446
Secondary ID [2] 287867 0
NCT00045032
Universal Trial Number (UTN)
Trial acronym
ANZ 0101 / BIG 1-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 38 0
Condition category
Condition code
Cancer 45 45 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised upon completion of definitive surgery and systemic adjuvant chemotherapy to receive no Herceptin® or Herceptin® for one year* or two years**. Patients will receive Herceptin by intravenous infusion at a dose of 8mg/kg on day 1, followed by maintenance dose of 6mg/kg three weeks later and thereafter every three weeks for a total of one or two years, or until disease recurrence.
* “1 year” of Herceptin® is defined as “12 calendar months of treatment from day 1 of 1st administration and 18 infusions maximum.
** “2 years” of Herceptin® is defined as “24 calendar months of treatment from day 1 of 1st administration and 35 infusions maximum.

If clinically indicated, all ER positive patients can receive systemic adjuvant hormonal therapy. Radiation therapy when indicated must have been completed prior to the start of Herceptin®.
Intervention code [1] 1242 0
Treatment: Drugs
Comparator / control treatment
1 or 2 years of Herceptin versus no Herceptin.
Control group
Active

Outcomes
Primary outcome [1] 73 0
To compare disease-free survival (DFS) in patients with HER2 overexpressing breast cancer who have been randomised to Herceptin? for one year versus no Herceptin?.
Timepoint [1] 73 0
Patients will be reviewed by clinicians for progression of disease every 3 months for the first 2 years and then 6 monthly in years 3-5 and yearly thereafter until 10 years from randomisation.
Primary outcome [2] 74 0
To compare DFS patients with HER2 overexpressing breast cancer who have been randomised to Herceptin? for two years versus no Herceptin?.
Timepoint [2] 74 0
Patients will be reviewed by clinicians for progression of disease every 3 months for the first 2 years and then 6 monthly in years 3-5 and yearly thereafter until 10 years from randomisation.
Secondary outcome [1] 136 0
To compare overall survival (OS) in patients randomised to i) Herceptin? for one year or no further therapy and to ii) Herceptin? for two years or no further therapy.
Timepoint [1] 136 0
Patients will be assessed by the clinician for survival, progression of disease, tolerability and side effects, and cardiac function 3 monthly in the first 2 years, 6 monthly years 3 to 5 and yearly thereafter until year 10 from randomisation.
Secondary outcome [2] 137 0
To compare relapse-free survival (RFS), distant disease free survival (DDFS), time to recurrence (TTR), time to distant recurrence (TTDR).
Timepoint [2] 137 0
Patients will be assessed by the clinician for survival, progression of disease, tolerability and side effects, and cardiac function 3 monthly in the first 2 years, 6 monthly years 3 to 5 and yearly thereafter until year 10 from randomisation.
Secondary outcome [3] 138 0
To evaluate the safety and tolerability of Herceptin?
Timepoint [3] 138 0
Patients will be assessed by the clinician for survival, progression of disease, tolerability and side effects, and cardiac function 3 monthly in the first 2 years, 6 monthly years 3 to 5 and yearly thereafter until year 10 from randomisation.
Secondary outcome [4] 139 0
To compare the incidence of cardiac dysfunction in patients treated and not treated with Herceptin?.
Timepoint [4] 139 0
Patients will be assessed by the clinician for survival, progression of disease, tolerability and side effects, and cardiac function 3 monthly in the first 2 years, 6 monthly years 3 to 5 and yearly thereafter until year 10 from randomisation.
Secondary outcome [5] 140 0
To compare outcomes (DFS, OS, RFS, DDFS, TTR, TTDR, cardiac safety, overall safety) of patients treated with Herceptin ? for one year compared with Herceptin ? for two years.
Timepoint [5] 140 0
Patients will be assessed by the clinician for survival, progression of disease, tolerability and side effects, and cardiac function 3 monthly in the first 2 years, 6 monthly years 3 to 5 and yearly thereafter until year 10 from randomisation.

Eligibility
Key inclusion criteria
Eastern Cooperative Oncology Group (ECOG) performance status = 1; Non-metastatic operable primary invasive adenocarcinoma of the breast that is: histologically confirmed, adequately excised, axillary node positive or negative, and tumour size =T1c according to TNM; Known hormone receptor status (ER/PgR or ER alone); Patient must have received at least four cycles of an approved (neo-) adjuvant chemotherapy regimen; Baseline LVEF = 55% measured by echocardiography or MUGA scan after completion of all (neo-) adjuvant chemotherapy and radiotherapy); Completion of radiotherapy for any patients undergoing radiotherapy; Overexpression of HER2 in the invasive component of the primary tumour, according to one of the following definitions: 3+ overexpression by IHC or 2+ overexpression by IHC AND fluorescence in situ hybridisation (FISH) test demonstrating c-erbB2 gene amplification, or c-erbB2 gene amplification by FISH; Completion of all necessary baseline lab and radiologic investigations; Signed written informed consent
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
History of any prior (ipsi- and/or contralateral) invasive breast carcinoma; Past or current history of malignant neoplasms, except for curative treated: basal and squamous cell carcinoma of the skin, in situ carcinoma of the cervix; Any “clinical” T4 tumour, including inflammatory breast cancer; Maximum cumulative dose of doxorubicin >360mg/m2 or maximum cumulative dose epirubicin > 720mg/m2 or any prior anthracyclines unrelated to the present breast cancer; (Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support; Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer; Patients with positive or suspicious internal mammary nodes identified by sentinel node technique which have not been irradiated or patients with supraclavicular lymph node involvement; Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for breast cancer; Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, immunotherapy, and bisphosphonate therapy; Serious cardiac illness or medical conditions including but not confined to: History of documented congestive heart failure (CHF), high-risk uncontrolled arrythmias, angina pectoris requiring antianginal medication, clinically significant valvular heart disease, evidence of transmural infarction on ECG, poorly controlled hypertension; Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness; Any of the following abnormal laboratory tests immediately prior to randomisation: serum bilirubin > 2.0 x upper limit of normal (ULN), alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2.5 x ULN, alkaline phosphatase (ALP) > 2.5 x ULN, serum creatinine > 2.0 x ULN, total white blood cell count (WBC) < 2500/mm3, absolute neutrophil count < 1500/mm3, platelets <100,000/mm3; Pregnant or lactating women; Women of childbearing potential or less than one year after menopause (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated stratified block
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
non-blinded
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2001
Actual
1/07/2002
Date of last participant enrolment
Anticipated
Actual
1/01/2005
Date of last data collection
Anticipated
Actual
4/01/2016
Sample size
Target
4482
Accrual to date
Final
5102
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 63 0
Self funded/Unfunded
Name [1] 63 0
BIG (Breast International Group)
Country [1] 63 0
Belgium
Funding source category [2] 64 0
Commercial sector/Industry
Name [2] 64 0
F.Hoffmann-La Roche Ltd
Country [2] 64 0
Switzerland
Primary sponsor type
Commercial sector/Industry
Name
F.Hoffmann-La Roche Ltd
Address
Konzern-Hauptsitz
Grenzacherstrasse 124
CH-4070 Basel
Country
Switzerland
Secondary sponsor category [1] 49 0
Other Collaborative groups
Name [1] 49 0
Breast International Group
Address [1] 49 0
Blvd de Waterloo 121
B-1000 Brussels
Country [1] 49 0
Belgium

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 382 0
Auckland Hospital
Ethics committee address [1] 382 0
Ethics committee country [1] 382 0
New Zealand
Date submitted for ethics approval [1] 382 0
Approval date [1] 382 0
Ethics approval number [1] 382 0
Ethics committee name [2] 383 0
Austin Health
Ethics committee address [2] 383 0
Ethics committee country [2] 383 0
Australia
Date submitted for ethics approval [2] 383 0
Approval date [2] 383 0
Ethics approval number [2] 383 0
Ethics committee name [3] 384 0
Border Medical Oncology
Ethics committee address [3] 384 0
Ethics committee country [3] 384 0
Australia
Date submitted for ethics approval [3] 384 0
Approval date [3] 384 0
01/12/2001
Ethics approval number [3] 384 0
Ethics committee name [4] 385 0
Box Hill Hospital
Ethics committee address [4] 385 0
Ethics committee country [4] 385 0
Australia
Date submitted for ethics approval [4] 385 0
Approval date [4] 385 0
Ethics approval number [4] 385 0
Ethics committee name [5] 386 0
Christchurch Hospital
Ethics committee address [5] 386 0
Ethics committee country [5] 386 0
New Zealand
Date submitted for ethics approval [5] 386 0
Approval date [5] 386 0
Ethics approval number [5] 386 0
Ethics committee name [6] 387 0
Dunedin Hospital
Ethics committee address [6] 387 0
Ethics committee country [6] 387 0
New Zealand
Date submitted for ethics approval [6] 387 0
Approval date [6] 387 0
Ethics approval number [6] 387 0
Ethics committee name [7] 388 0
Frankston Hospital
Ethics committee address [7] 388 0
Ethics committee country [7] 388 0
Australia
Date submitted for ethics approval [7] 388 0
Approval date [7] 388 0
Ethics approval number [7] 388 0
Ethics committee name [8] 389 0
Liverpool Hospital
Ethics committee address [8] 389 0
Ethics committee country [8] 389 0
Australia
Date submitted for ethics approval [8] 389 0
Approval date [8] 389 0
Ethics approval number [8] 389 0
Ethics committee name [9] 390 0
Maroondah Hospital
Ethics committee address [9] 390 0
Ethics committee country [9] 390 0
Australia
Date submitted for ethics approval [9] 390 0
Approval date [9] 390 0
Ethics approval number [9] 390 0
Ethics committee name [10] 391 0
Mater Hospital
Ethics committee address [10] 391 0
Ethics committee country [10] 391 0
Australia
Date submitted for ethics approval [10] 391 0
Approval date [10] 391 0
Ethics approval number [10] 391 0
Ethics committee name [11] 392 0
Mercey Private
Ethics committee address [11] 392 0
Ethics committee country [11] 392 0
Australia
Date submitted for ethics approval [11] 392 0
Approval date [11] 392 0
Ethics approval number [11] 392 0
Ethics committee name [12] 393 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [12] 393 0
Ethics committee country [12] 393 0
Australia
Date submitted for ethics approval [12] 393 0
Approval date [12] 393 0
Ethics approval number [12] 393 0
Ethics committee name [13] 394 0
Palmerston North Hospital
Ethics committee address [13] 394 0
Ethics committee country [13] 394 0
New Zealand
Date submitted for ethics approval [13] 394 0
Approval date [13] 394 0
Ethics approval number [13] 394 0
Ethics committee name [14] 395 0
Peter MacCallum Cancer Centre
Ethics committee address [14] 395 0
Ethics committee country [14] 395 0
Australia
Date submitted for ethics approval [14] 395 0
Approval date [14] 395 0
Ethics approval number [14] 395 0
Ethics committee name [15] 396 0
Queen Elizabeth Hospital
Ethics committee address [15] 396 0
Ethics committee country [15] 396 0
Australia
Date submitted for ethics approval [15] 396 0
Approval date [15] 396 0
Ethics approval number [15] 396 0
Ethics committee name [16] 397 0
Royal Melbourne Hospital
Ethics committee address [16] 397 0
Ethics committee country [16] 397 0
Australia
Date submitted for ethics approval [16] 397 0
Approval date [16] 397 0
Ethics approval number [16] 397 0
Ethics committee name [17] 398 0
Sir Charles Gairdner Hospital
Ethics committee address [17] 398 0
Ethics committee country [17] 398 0
Australia
Date submitted for ethics approval [17] 398 0
Approval date [17] 398 0
Ethics approval number [17] 398 0
Ethics committee name [18] 399 0
Wellington Hospital
Ethics committee address [18] 399 0
Ethics committee country [18] 399 0
New Zealand
Date submitted for ethics approval [18] 399 0
Approval date [18] 399 0
Ethics approval number [18] 399 0
Ethics committee name [19] 400 0
Western Hosptial
Ethics committee address [19] 400 0
Ethics committee country [19] 400 0
Australia
Date submitted for ethics approval [19] 400 0
Approval date [19] 400 0
Ethics approval number [19] 400 0
Ethics committee name [20] 401 0
Westmead Hospital
Ethics committee address [20] 401 0
Ethics committee country [20] 401 0
Australia
Date submitted for ethics approval [20] 401 0
Approval date [20] 401 0
Ethics approval number [20] 401 0

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

Contacts
Principal investigator
Name 35775 0
A/Prof Nicholas Wilcken
Address 35775 0
Department of Medical Oncology & Palliative Care
Westmead Hospital
Darcy Road (cnr Hawkesbury Road)
WESTMEAD NSW 2145
Country 35775 0
Australia
Phone 35775 0
+61 (02) 9845-5200
Fax 35775 0
Email 35775 0
[email protected]
Contact person for public queries
Name 10431 0
Corinna Beckmore
Address 10431 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 10431 0
Australia
Phone 10431 0
+61 2 4925 3068
Fax 10431 0
+61 2 49850141
Email 10431 0
[email protected]
Contact person for scientific queries
Name 1359 0
John F Forbes
Address 1359 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 1359 0
Australia
Phone 1359 0
+61 2 4985 0113
Fax 1359 0
+61 2 4960 1539
Email 1359 0
[email protected]

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