A Study of Subcutaneously Administered Herceptin (Trastuz... | NCT01928615

NCT01928615

ID	Type	Description	Link
2013-001023-39	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

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No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Trastuzumab - Thigh first, then upper arm	Experimental	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).	Drug: Trastuzumab - intravenous solution Drug: Trastuzumab - subcutaneous solution Drug: Chemotherapy
Trastuzumab - Upper arm first, then thigh	Experimental	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Participants could also receive a maximum of 6 cycles of standard chemotherapy for early breast cancer (neo-adjuvant or adjuvant) in the run-in phase. Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).	Drug: Trastuzumab - intravenous solution Drug: Trastuzumab - subcutaneous solution Drug: Chemotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Trastuzumab - intravenous solution	Drug	Trastuzumab was supplied as a powder to be reconstituted as a solution for intravenous infusion.	Trastuzumab - Thigh first, then upper arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Quality of Life Score	Participants rated their quality of life on a visual analog scale (VAS) at the end of each cycle for Cycles 7-14. The left-end of the VAS represented the lowest-rated quality of life and the right-end of the VAS represented the highest-rated quality of life. Both the mean ratings for injections into the thigh and the upper arm and the minimum ratings for during injections into the thigh and the upper arm are reported. Quality of life scores ranged from 1 to 100 with a higher score indicating a better rated quality of life.	Cycles 7-14 (Weeks 19-42, 24 weeks total)

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival	Overall survival was defined as the time in months from Baseline to death from any cause.	Baseline to the end of the study (up to 54 weeks)
Disease-free Survival	Disease-free survival was defined as the time in months from Baseline to disease recurrence or death, whichever occurred first.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Female and male patients ≥ years of age.
HER2-positive early breast cancer.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Hormonal therapy will be allowed as per institutional guidelines.
Patients must be Herceptin (trastuzumab) naïve.
Left ventricular ejection fraction (LVEF) of ≥ 55%.
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast.
No evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy, or during concurrent chemotherapy (neo-adjuvant or adjuvant).
Use of concurrent curative radiotherapy will be permitted.

Exclusion Criteria:

History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and patients with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible.
Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.
Patients with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness.
Serious cardiac illness or medical conditions that would preclude the use of Herceptin, specifically, a history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), or diagnosed poorly controlled hypertension.
Pregnant or lactating women.
Women of childbearing potential and male patients with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment.
Concurrent enrollment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy, and immunotherapy, within 28 days prior to the first dose of study treatment.
Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin including hyaluronidase, or a history of severe allergic or immunological reactions, eg, difficult to control asthma.
Inadequate bone marrow, hepatic, or renal function.

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

References Module

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IPD Sharing Statement Module

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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Trastuzumab	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants were randomized to receive trastuzumab 600 mg subcutaneously every 3 weeks in the thigh and upper arm in a cross-over design for a total of 24 weeks (Cycles 7-14). They received trastuzumab either in the thigh first for 4 cycles (Cycles 7-10) followed by trastuzumab in the upper arm for 4 cycles (Cycles 11-14) or the upper arm first (Cycles 7-10) followed by the thigh (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

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No data is available for this block.

Document Section

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Derived Section

Miscellaneous Info Module

Submission Tracking

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No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Trastuzumab - Upper arm first, then thigh

Full analysis set: All participants who were enrolled in the study.

Arm/Group Information

ID	Title	Description
BG000	Trastuzumab	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants were randomized to receive trastuzumab 600 mg subcutaneously every 3 weeks in the thigh and upper arm in a cross-over design for a total of 24 weeks (Cycles 7-14). They received trastuzumab either in the thigh first for 4 cycles (Cycles 7-10) followed by trastuzumab in the upper arm for 4 cycles (Cycles 11-14) or the upper arm first (Cycles 7-10) followed by the thigh (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Units	Counts
Participants	BG0002

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
Female	BG0002
Male	BG0000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Quality of Life Score

Participants rated their quality of life on a visual analog scale (VAS) at the end of each cycle for Cycles 7-14. The left-end of the VAS represented the lowest-rated quality of life and the right-end of the VAS represented the highest-rated quality of life. Both the mean ratings for injections into the thigh and the upper arm and the minimum ratings for during injections into the thigh and the upper arm are reported. Quality of life scores ranged from 1 to 100 with a higher score indicating a better rated quality of life.

Modified intent-to-treat population: All participants who received at least 1 dose of study medication and who have at least 1 quality of life score in each treatment period (Cycles 7-10 and Cycle 11-14).

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

Cycles 7-14 (Weeks 19-42, 24 weeks total)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Units	Counts
Participants	OG0000 OG0010

Secondary

Overall Survival

Overall survival was defined as the time in months from Baseline to death from any cause.

Intent-to-treat population: All participants who received at least 1 dose of study medication.

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

Baseline to the end of the study (up to 54 weeks)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Secondary

Disease-free Survival

Disease-free survival was defined as the time in months from Baseline to disease recurrence or death, whichever occurred first.

Intent-to-treat population: All participants who received at least 1 dose of study medication.

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

Baseline to the end of the study (up to 54 weeks)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Secondary

Health Care Provider's Satisfaction With the Injection Site

The health care provider for each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.

Intent-to-treat population: All participants who received at least 1 dose of study medication.

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

End of Cycles 10 and 14 (Weeks 30 and 42)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Secondary

Participant's Satisfaction With the Injection Site

Each participant was asked to rate their satisfaction with the 2 injection sites, thigh and upper arm, on a scale of 1 to 10, where 10 represents greater satisfaction. Ratings were made at the end of Cycles 10 and 14.

Intent-to-treat population: All participants who received at least 1 dose of study medication.

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

End of Cycles 10 and 14 (Weeks 30 and 42)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Secondary

Percentage of Participants Preferring Each Injection Site

Participants were asked which of the 2 injection sites was their preferred site at the end of Cycle 14.

Intent-to-treat population: All participants who received at least 1 dose of study medication.

Due to the low enrollment (n = 2) and premature termination of the study, the Outcome Measure was not analyzed.

End of Cycle 14 (Week 42)

ID	Title	Description
OG000	Trastuzumab - Thigh First, Then Upper Arm	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the thigh for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the upper arm for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).
OG001	Trastuzumab - Upper Arm First, Then Thigh	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants received trastuzumab 600 mg subcutaneously (SC) every 3 weeks into the upper arm for 12 weeks (Cycles 7-10) followed by trastuzumab 600 mg SC every 3 weeks into the thigh for 12 weeks (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Trastuzumab	In the run-in phase, participants received trastuzumab intravenously every 3 weeks for 18 weeks (Cycles 1-6). They first received trastuzumab 8 mg/kg once (Cycle 1) followed by trastuzumab 6 mg/kg 5 times for 15 weeks (Cycles 2-6). Following the run-in phase, participants were randomized to receive trastuzumab 600 mg subcutaneously every 3 weeks in the thigh and upper arm in a cross-over design for a total of 24 weeks (Cycles 7-14). They received trastuzumab either in the thigh first for 4 cycles (Cycles 7-10) followed by trastuzumab in the upper arm for 4 cycles (Cycles 11-14) or the upper arm first (Cycles 7-10) followed by the thigh (Cycles 11-14). In Cycles 15-18, participants received trastuzumab 600 mg SC every 3 weeks into either the thigh or the upper arm (participant's choice) for 12 weeks (Cycles 15-18).			0	2	1	2

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Common cold	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment		EG0001 affected2 at risk

Title	Organization	Phone	Extension	Email
Medical Communications	Hoffmann-La Roche	800 821-8590		genentech@druginfo.com

ID	Term
D001943	Breast Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D000068878	Trastuzumab
D004358	Drug Therapy

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D013812	Therapeutics

Facility	Status	City	State	ZIP	Country	Contacts
		Innsbruck		6020	Austria