A Safety and Tolerability Study of Assisted and Self-Administered Subcutaneous (SC) Herceptin (Trastuzumab) as Adjuvant Therapy in Early Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

Phase 3

Completed

Conditions: Breast Neoplasms

Interventions: Drug: Herceptin

Registration Number: NCT01566721

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This multicenter, two-cohort, non-randomized, open-label study will evaluate the safety and tolerability of assisted and self-administered SC Herceptin as adjuvant therapy in participants with early HER2-positive breast cancer following tumor excision. Participants will receive Herceptin 600 milligrams (mg) SC every 3 weeks for 18 cycles, either by an assisted administration using a conventional syringe and needle/vial formulation (Cohort A) or with assisted and self-administration using a single-use injection device (SID) in selected participants (Cohort B).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2577

Inclusion Criteria

Histologically confirmed early invasive HER2-positive carcinoma of the breast with no evidence of residual, locally recurrent, or metastatic disease and defined as clinical Stage I to IIIC that is eligible for treatment with Herceptin
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Screening left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55%

Exclusion Criteria

Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent
History of other malignancy except for curatively treated carcinoma in situ of the cervix, basal cell carcinoma, or curatively treated malignancies (other than breast cancer) where the participant has been disease-free for at least 5 years
Past history of ductal carcinoma in situ treated with any systemic therapy or with radiation therapy to the ipsilateral breast where invasive cancer subsequently developed
Metastatic disease
Inadequate bone marrow, hepatic, or renal function
Serious cardiac or cardiovascular disease including uncontrolled hypertension or history of hypertensive crisis or hypertensive encephalopathy
History of severe allergic or immunological reactions, such as difficult-to-control asthma
Pregnant or lactating women

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A: SC Herceptin by Needle/Syringe	Herceptin	Participants will receive SC Herceptin by an assisted administration using a conventional syringe and needle/vial formulation.
Cohort B: SC Herceptin by SID	Herceptin	Participants will receive SC Herceptin with assisted and/or self-administered use of an SID. The first administration will be performed by a trained healthcare professional. If well tolerated and the participant is willing and judged competent to perform self-administration, subsequent administration of SC Herceptin may be performed by the participant.

Primary Outcome Measures

Name	Time	Method
Number of Herceptin Cycles Received	From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)	Participants were planned to receive a total of 18 cycles of SC Herceptin. The median number of cycles actually received was reported.
Percentage of Participants With a Grade 3 or Higher AE During the Treatment Period	From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)	Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. AEs were graded according to National Cancer Institute Common Terminology Criteria Version 4.0. Grade 3 AEs were those considered severe or medically significant but not immediately life-threatening. Grade 4 AEs were those considered life-threatening and/or for which urgent intervention was indicated. Grade 5 AEs were those resulting in death. The percentage of participants with a Grade 3 or higher (i.e., Grade 3 to 5) AE during the treatment period was reported.
Percentage of Participants by Total Number of Herceptin Cycles Received	From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)	Participants were planned to receive a total of 18 cycles of SC Herceptin. The percentage of participants was reported by the total number of cycles actually received. Because the data are presented non-cumulatively, this table reflects participant distribution by the highest number of cycles received.
Percentage of Participants Who Received Concomitant Cancer Therapy	From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)	Concomitant cancer treatment included chemotherapy, radiotherapy, and hormone therapy administered during the study. The percentage of participants who received any of these concomitant therapies was reported.
Percentage of Participants Who Received Concomitant Non-Cancer Therapy	From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)	Concomitant non-cancer treatment included any pharmacologic interventions administered during the study other than chemotherapy, radiotherapy, or hormone therapy. The percentage of participants who received any concomitant non-cancer therapies was reported.
Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period	From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)	Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported.
Percentage of Participants With Treatment Interruption Due to an AE	From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)	Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with SC Herceptin treatment interrupted to assess or treat AEs was reported.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Died During the Safety Follow-up Period	From Baseline to Time of Event, Safety Follow-Up Period (Up to 6 Years)	The percentage of participants who died from any cause was reported during the safety follow-up period.
Percentage of Participants Who Died by Data Cutoff of 10 March 2015	From Baseline to time of event (maximum follow-up approximately 3 years as of data cutoff of 10 March 2015)	The percentage of participants who died from any cause was reported.
Disease-Free Survival Rate	From Baseline to time of event (up to approximately 8 years)	DFS is defined as the time from first dose of SC Herceptin to the first event of local, regional or distant recurrence, contralateral invasive breast cancer (including ipsilateral ductal carcinoma in situ) or death due to any cause. Time from the date of first dose to any DFS event was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.
Overall Survival Rate	From Baseline to Time of Event (Up to Approximately 6 Years)	Overall survival was defined as the time from randomization to death from any cause. Time from the date of randomization to the date of death was expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at the last assessment date.
Percentage of Participants by Item Response to SID Satisfaction Questionnaire	Cycle 4 (cycle length 3 weeks) and last safety follow-up (LSFU) (approximately 1 year)	The SID satisfaction questionnaire was administered twice during the study and asked participants to respond to five statements using a Likert scale from "Strongly Disagree" to "Strongly Agree". Questionnaire items were as follows: "I felt comfortable injecting the study drug by myself" (Comfortable), "The SID was convenient and easy to use" (Easy to Use), "I am confident giving myself an injection in the thigh with the SID" (Confident), "Taking all things into account I find self-administration using the SID satisfactory" (Satisfactory), "If given the opportunity I would choose to continue self-injecting the study drug using the SID in the future" (Continue). Participants could only select one response per questionnaire item. There was no calculation of any score, but rather, descriptive summaries were generated by item response. The percentage of participants was reported by the response given for each item on the SID satisfaction questionnaire.

Trial Locations

Locations (437): University "Mother Theresa" Hospital Center; Oncology Department
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Tirana, Albania
CPMC; Service d'Oncologie Médicale
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Algiers, Algeria
Fundación CENIT para la Investigación en Neurociencias
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Buenos Aires, Argentina
Hospital Britanico; Oncologia
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Buenos Aires, Argentina
Instituto De Investigaciones Clinicas Zarate
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Zarate, Argentina
Chris O'Brien Lifehouse
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Camperdown, New South Wales, Australia
St George Hospital; Cancer Care Centre
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Kogarah, New South Wales, Australia
Prince of Wales Hospital; Oncology
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Randwick, New South Wales, Australia
Princess Alexandra Hospital; Division of Cancer Services
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Woolloongabba, Queensland, Australia
Queen Elizabeth Hospital; Medical Oncology
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Woodville South, South Australia, Australia
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University "Mother Theresa" Hospital Center; Oncology Department
🇦🇱Tirana, Albania