A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study of AryoTrust™ (AryogenTrastuzumab) efficacy and safety in Human Epidermal Growth Factor Receptor 2–Positive breast cancer in comparison to Herceptin® (Genentech/Roche) control.
This is a Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study with a 1:1 allocation. This trial will be initiated from 2016 and recruit patients from Imam Khomeini Hospital Complex. Probable variation of eligibility criteria and evaluation criteria will be resolved through investigator meetings.
All patients are scheduled to receive AC-Docetaxel+Trastuzumab regimen. Using a non-inferiority margin of 0.25 for the primary end point, a sample size of 48 in each group achieves. Considering 0.10 losses to follow up, final sample size is 54 in each group. The randomization is based on stratified blocked randomization, which strata are age (<50 years vs ≥50 years) and stage of disease (stage III vs stages II). The allocation of randomization code will be performed after all inclusion criteria and none of exclusion criteria were met and signing the informed consent was done. To collect accurate and valid data, a standard CRF will be applied. Treatment differences will be calculated for outcomes. Data analysis is performed using non-inferiority analysis. Any modifications to the protocol which may impact on the conduct of the study, will require a formal amendment to the protocol.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT201606226135N7
Registration date:2016-06-25, 1395/04/05
Registration timing:prospective
Last update:
Update count:2
Registration date
2016-06-25, 1395/04/05
Registrant information
Name
Hamed Hosseini
Name of organization / entity
Clinical Trial Center (CTC),Tehran University of Medical Sciences (TUMS)
Country
Iran (Islamic Republic of)
Phone
+98 21 8896 3546
Email address
hhosseini@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
All expenses of this study including patients’ treatment and medicines, study conduct and performing and research related injuries compensation will be provided by Aryogen pharmed co.
Expected recruitment start date
2016-07-02, 1395/04/12
Expected recruitment end date
2017-07-03, 1396/04/12
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study of AryoTrust™ (AryogenTrastuzumab) efficacy and safety in Human Epidermal Growth Factor Receptor 2–Positive breast cancer in comparison to Herceptin® (Genentech/Roche) control.
Public title
not inferior of efficacy and side effects in Aryo Trust™ (Aryogen trastuzumab) vs Herceptin® (Genentech/Roche trastuzumab) in term of pCR rate.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
• 18-55 years old female patients
• Patients with newly diagnosed stage III(locally advanced) or in-operable stage II (due to sizes larger than 5 cm or high tumor to breast ratio) tumors are candidates for participation. (Appendix 1)
• Willing and able to sign an informed consent
• Pathological diagnosis of adenocarcinoma of the breast
• ECOG status of 0-1
• With any ER/PR status
• HER2 positive (Immunohistochemical (IHC) 3+ intensity, amplification of the HER2 gene on fluorescence in situ hybridization (FISH+ ) or HER2 positive results of Chromogenic in situ hybridization (CISH)).
o NOTE: ductal carcinoma in situ (DCIS) components should not be consideredin the determination of degree of IHC staining or FISH amplification.
Exclusion Criteria
• Clinical or radiologic evidence of metastatic disease
• History of any other malignancy including previous breast cancer, second non-breast malignant disease
• History of previous chemotherapy
• Left ventricular ejection fraction [LVEF] <55% confirmed by echo cardiogram within 3 months before registration, Any prior myocardial infarction, History of documented congestive heart failure (CHF),Any prior history of arrhythmia or cardiac valvular disease requiring medications or clinically significant,Current use of medications for treatment of angina pectoris, Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg), A severe conduction abnormality (having pacemaker or diagnosed by the ECG) and any other significant cardiovascular disease.
• Hematologic abnormalities including baseline Absolute NeutrophilCount (ANC) of≤1,500/µL or platelet count ≤ 100,000/µL
• Liver dysfunction including : (baseline)
o Alanine amino transferase(ALT) and/or aspartate amino transferase (AST)≥3 Upper Limit Normal (ULN)
o Alkaline phosphatase (ALP)≥3 ͯ ULN
o serum total bilirubin > 1.5 ULN
• Renal dysfunction, defined as serum creatinine≥2.5 mg/dL
• Pregnant, lactating women or women of childbearing potential who are not willing to use adequate contraception
Age
From 18 years old to 55 years old
Gender
Female
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
108
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Triple blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Tehran university of medical science, Medical Ethics Committee
Street address
Tehran university of medical science
City
Tehran
Postal code
Approval date
2016-06-22, 1395/04/02
Ethics committee reference number
it.tums.rec.1395.2730
Health conditions studied
1
Description of health condition studied
breast cancer patients with HER2-positive
ICD-10 code
C50
ICD-10 code description
Malignant neoplasm of breast
Primary outcomes
1
Description
pathologic Complete Response (pCR)
Timepoint
following completion of neoadjuvant systemic therapy
Method of measurement
the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes
Secondary outcomes
1
Description
clinicalCompleteResponse (cCR)
Timepoint
Disappearance of all target lesions
Method of measurement
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10 mm
2
Description
clinical Partial Response (cPR)
Timepoint
Partial disappearance of target lesions
Method of measurement
At least a 30% decrease in the sum of diameters of target lesions
3
Description
clinicallyStable Disease (cSD)
Timepoint
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
Method of measurement
lymph nodes pathology
4
Description
clinical Progressive Disease (cPD)
Timepoint
at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Method of measurement
pathology
5
Description
clinical Objective Response(cOR)
Timepoint
Observe clinical response
Method of measurement
(cOR= cCR+ cPR)
6
Description
breast conservation rate
Timepoint
The end of treatment
Method of measurement
number of mastectomy patients vs to the total patients
Intervention groups
1
Description
Intervention group:
All patients are scheduled to receive AC-Docetaxel+Trastuzumab regimen as detailed bellow:
Doxorubicin + Cyclophosphamide phase:
Cycle length: 21 days.
Total cycles: 4 cycles
Doxorubicin, 60 mg/m2 IV, 1 per day
Cyclophosphamide,600 mg/m2 IV, 1 per day
Docetaxel + AryoTrust™ phase:
Docetaxel + AryoTrust™ phase:
Cycle length: 21 days.
Total cycles: 4 cycles
Docetaxel + AryoTrust™ phase:
Cycle length: 21 days.
Total cycles: 4 cycles
Docetaxel, 100 mg/m2 IV
AryoTrust™, 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles
Category
Treatment - Drugs
2
Description
Control Group:
Doxorubicin + Cyclophosphamide phase:
Cycle length: 21 days.
Total cycles: 4 cycles
Doxorubicin,60 mg/m2 IV, 1 day
Cyclophosphamide, 600 mg/m2 IV, 1 day
Docetaxel+ trastuzumab phase:
Cycle length: 21 days.
Total cycles: 4 cycles
Docetaxel, 100 mg/m2 IV
Herceptin®, 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Complex
Full name of responsible person
Street address
Keshavarz Blvd.
City
Tehran
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Aryogen pharmed Company
Full name of responsible person
Parisa Nejat
Street address
Cross Tajbakhsh Street, 24th Kilometer Makhsous, Tehran - Iran . AryoGen Biopharma Co.
City
Tehran
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Aryogen pharmed Company
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
Aryogen pharmed Company
Full name of responsible person
Parisa Nejat
Position
master of science in clinical laboratory
Other areas of specialty/work
Street address
Shahrak gharb- Farahzadi Blvd., West Dadman Blvd.,derakhti St,-Khorasan- dead end i, No. 2
City
Tehran
Postal code
Phone
+98 21 8808 8821
Fax
Email
Contact@Aryogen.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran university of medical science
Full name of responsible person
Reza Safaie Nodehi
Position
Assistant Professor, Internal Medicine - Hematology and Oncology specialist
Other areas of specialty/work
Street address
Keshavarz Blvd., Imam Khomeini Hospital Complex
City
Tehran
Postal code
Phone
+98 21669350649
Fax
Email
safano1334@gmail.com
Web page address
Person responsible for updating data
Contact
Name of organization / entity
Tehran university of medical science
Full name of responsible person
Ayat Ahmadi
Position
PHD of epidemiology
Other areas of specialty/work
Street address
Tehran university of medical science
City
Tehran
Postal code
Phone
00
Fax
Email
Web page address
Sharing plan
Deidentified Individual Participant Data Set (IPD)