Protocol summary

Study aim
Comparison of efficacy and safety of Padynex and trastuzumab in women with HER2 positive metastatic breast cancer
Design
A randomised controlled trial, Phase II, two-arm, open-label with a group of 150 patients. In this study, women with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer will receive a 1:2 ratio of padynex and trastuzumab, respectively. Randomization is based on the method of random permuted blocks.
Settings and conduct
Shohadaye Tajrish hospital, Firoozgar hospital; This study is an open label clinical trial; In first group, patients will receive Padynex at a dose of 3.6 mg per kilogram of body weight every 3 weeks for 6 cycles, the second group will be assigned to the treatment of trastuzumab.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Women aged 18-75 years HER2+ Metastatic breast cancer (Metastasis to intraperitoneal solid organs, lungs, pleura, or multiple bones) Exclusion criteria: History of type 1 allergic/anaphylactic infusion reactions to any component of the PADYNEX formulation. History of treatment with trastuzumab-emtansine. Patients with locally advanced breast cancer and non metastatic. Patients with brain metastasis.
Intervention groups
Intervention group 1 includes patients with HER2+ metastatic breast cancer who will receive Padynex. Intervention group 2 includes patients with HER2+ metastatic breast cancer who will receive trastuzumab.
Main outcome variables
Objective response rate; gastrointestinal disorders such as vomiting, constipation and diarrhea; pain; blood disorders such as Neutropenia, anemia, leukopenia and thrombocytopenia; Alanine aminotransferase levels, aspartate aminotransferase levels; fever; peripheral neuropathy.

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20201223049810N1
Registration date: 2021-02-02, 1399/11/14
Registration timing: registered_while_recruiting

Last update: 2021-02-02, 1399/11/14
Update count: 0
Registration date
2021-02-02, 1399/11/14
Registrant information
Name
Hanieh yadollahi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8864 9082
Email address
h.yadollahi@nanodaru.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-01-20, 1399/11/01
Expected recruitment end date
2023-01-21, 1401/11/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of efficacy and safety of PADYNEX (Trastuzumab-emtansine, T-DM1, manufactured by Nano Daru Pajuhan Pardis) in women with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer: A randomised controlled trial, two-arm, open-label.
Public title
Evaluation of efficacy and safety of PADYNEX in women with HER2+ metastatic breast cancer
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Women aged 18-75 years Metastatic breast cancer (Metastasis to intraperitoneal solid organs, lungs, pleura, or multiple bones) Based on histological, cytological and imaging results. HER2+ (immunohistochemistry 3+, HER2 gene amplification in fluorescence in situ hybridization positive or positive HER2 result in Chromogenic in situ hybridization). Patients with measurable disease based on Response Evaluation Criteria in Solid Tumors, version 1.1, (the minimum size of a measurable lesion at baseline should be no less than double the slice thickness (when CT scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness)). Life expectancy of more than 12 weeks based on a physician or treatment team estimate. Acceptable clinical test results at the beginning of the study based on the normal range of the reporting laboratory An Eastern Cooperative Oncology Group performance status of 0–2 All the patients provided written informed consent.
Exclusion criteria:
History of type 1 allergic/anaphylactic infusion reactions to any component of the PADYNEX formulation History of treatment with trastuzumab-emtansine Patients with locally advanced breast cancer and non metastatic History of second non-breast cancer in last 5 year Patients with brain metastasis Serious concurrent disease (chronic kidney disease stage 4,5, hepatic impairment child pugh class c, bronchiectasis, severe chronic obstructive pulmonary disease, severe asthma, pulmonary fibrosis) Peripheral neuropathy of grade 3 or worse (as per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0) Left ventricular ejection fraction lower than 50% (as measured by echocardiography) within previous 3 months, myocardial infarction or congestive heart failure within previous 6 months, high-risk uncontrolled arrhythmias; clinically significant valvular disease; concomitant medication for the treatment of unstable angina, uncontrolled blood pressure (higher than 200/100 mmHg), severe electrical conduction defect (having a pacemaker or electrocardiogram diagnosis) or Any other significant heart disease. Blood disorders such as baseline absolute neutrophil count lower or equal to 1,500 per microliter or platelet count lower or equal to 100,000 per microliter. Alanine aminotransferase/ aspartate aminotransferase higher or equal to 2.5 upper limit of normal. Pregnancy, breast-feeding, and women of childbearing potential not using contraception.
Age
From 18 years old to 75 years old
Gender
Female
Phase
2
Groups that have been masked
No information
Sample size
Target sample size: 150
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization is based on the method of random permuted blocks. In this study, the following four blocks will be used: AABB, ABAB, ABBA, BBAA, BABA, BAAB First, one of these six blocks is randomly selected and individuals are assigned to two groups based on it (for example, if the first selected block is ABAB, the first patient is group A, the second patient is group B, the third patient is group A, and the fourth patient is assigned to group B. Then the next four blocks are selected and this process will continue until the sample is completed. Randomization will be performed using SAS statistical software version 9.4.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Shahid Beheshti University of Medical Sciences
Street address
Third Floor, Faculty of Medicine, Next to Taleghani Hospital, Evin, Shahid Chamran Highway, Tehran
City
Tehran
Province
Tehran
Postal code
1985717434
Approval date
2020-12-03, 1399/09/13
Ethics committee reference number
IR.SBMU.CRC.REC.1399.030

Health conditions studied

1

Description of health condition studied
Human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer
ICD-10 code
C50
ICD-10 code description
Malignant neoplasm of breast

Primary outcomes

1

Description
Objective Response Rate
Timepoint
before starting treatment, 77 and 105 day after starting treatment
Method of measurement
computerized tomography scan or Magnetic resonance imaging, According to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1)

Secondary outcomes

1

Description
pain score
Timepoint
Pain score will be assessed at 21, 42, 63, 84, 105 and 126 days after starting the treatment.
Method of measurement
The grade (severity) of pain will be assessed by visual analog scale.

2

Description
Vomiting
Timepoint
The grade of Vomiting will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Case report form

3

Description
Diarrhea
Timepoint
The grade of diarrhea will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Case report form

4

Description
Constipation
Timepoint
The grade of constipation will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Case report form

5

Description
Neutropenia
Timepoint
The grade of neutropenia will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Taking a blood test from the patient; Nihon Kodhen ES Hematology Analyzer based on flow cytometry method

6

Description
Anemia
Timepoint
The grade of anemia will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Taking a blood test from the patient; Nihon Kodhen ES Hematology Analyzer based on flow cytometry method.

7

Description
Leukopenia
Timepoint
The grade of leukopenia will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Taking a blood test from the patient; Nihon Kodhen ES Hematology Analyzer based on flow cytometry method

8

Description
Thrombocytopenia
Timepoint
The grade of thrombocytopenia will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Taking a blood test from the patient; Nihon Kodhen ES Hematology Analyzer based on flow cytometry method

9

Description
Alanine aminotransferase levels
Timepoint
The grade of alanine aminotransferase will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
BT3500 analyzer based on enzymatic method

10

Description
Aspartate aminotransferase levels
Timepoint
The grade of aspartate aminotransferase, will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
BT3500 analyzer based on enzymatic method

11

Description
Fever
Timepoint
The grade of fever will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Thermometer

12

Description
Peripheral neuropathy
Timepoint
The grade of peripheral neuropathy will be assessed at 21, 42, 63, 84, 105 and 126 days after starting treatment.
Method of measurement
Case report form

Intervention groups

1

Description
Intervention group: 50 women with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer, receiving Padynex (trastuzumab-emtansine, T-DM1 manufactured by Nano Daru Pajuhan Pardis) at a dose of 3.6 mg per kg by intravenous infusion every three weeks for 6 cycles.
Category
Treatment - Drugs

2

Description
Control group: 100 women with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer, receiving trastuzumab; Loading dose of 8 mg per kg body weight of patients, and 3 weeks after loading dose, maintenance dose of 6 mg per kg body weight by intravenous infusion, every three weeks for 6 cycles.
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Firoozgar hospital
Full name of responsible person
Mohsen Razavi
Street address
Firoozgar hospital, Behafarin St., Karimkhan Zand St., Valiasr Sq., Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
۱۵۹۳۷۴۷۸۱۱
Phone
+98 21 8214 1000
Email
h_firoozgar@yahoo.com

2

Recruitment center
Name of recruitment center
Shohadaye Tajrish hospital
Full name of responsible person
Hamidreza Mirzaei
Street address
Shohadaye Tajrish Hospital, Tajrish Sq., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1989934148
Phone
+98 21 25719
Email
pr_shohada@sbmu.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Nano Daru Pajuhan Pardis Company
Full name of responsible person
Hanieh Yadollahi
Street address
NO. 4, Northern Tak Ave., Attar St., Vanak Sq., Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1994754953
Phone
+98 21 8864 9082
Email
h.yadollahi@nanodaru.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Nano Daru Pajuhan Pardis Company
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry

Person responsible for general inquiries

Contact
Name of organization / entity
Nano Daru Pajuhan Pardis Company
Full name of responsible person
Hanieh Yadollahi
Position
Pharmacist
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
NO. 4, Northern Tak Ave., Attar St., Vanak Sq., Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1994754953
Phone
+98 21 8864 9082
Email
h.yadollahi@nanodaru.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Nano Daru Pajuhan Pardis Company
Full name of responsible person
Hanieh Yadollahi
Position
pharmacist
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
NO. 4, Northern Tak Ave., Attar St., Vanak Sq., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1994754953
Phone
+98 21 8864 9082
Email
asalshimi2020@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Nano Daru Pajuhan Pardis Company
Full name of responsible person
Hanieh Yadollahi
Position
Pharmacist
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
NO. 4, Northern Tak Ave., Attar St., Vanak Sq., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1994754953
Phone
+98 21 8864 9082
Email
asalshimi2020@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
In the participants data file, only part of the data will be shared as the main outcome.
When the data will become available and for how long
1 year after publication of result
To whom data/document is available
Researchers working in academic and scientific institutions
Under which criteria data/document could be used
At the request of researchers working in academic and scientific institutions
From where data/document is obtainable
Hanieh Yadollahi Email: h.yadollahi@nanodaru.com
What processes are involved for a request to access data/document
Up to 3 months after request
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