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A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (SCHEARLY)

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ClinicalTrials.gov Identifier: NCT01940497
Recruitment Status : Completed
First Posted : September 12, 2013
Results First Posted : July 2, 2017
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This non-randomized, multicenter, open-label study will assess the safety and efficacy of subcutaneously administered trastuzumab in participants with early and locally advanced HER2-positive breast cancer in two sequential cohorts. First 120 participants will be treated with subcutaneous (SC) trastuzumab 600 milligrams (mg) vial (Cohort A) and the subsequent 120 participants will be treated with SC trastuzumab prefilled single use injection device (SID) (Cohort B). Participants from each cohort will receive neoadjuvant or adjuvant chemotherapy consisting of doxorubicin every 3 weeks (q3w) (1 cycle) for 4 cycles followed by paclitaxel weekly or docetaxel every 3 weeks (q3w) in combination with SC trastuzumab (600 mg) q3w for 4 cycles and a further 14 cycles of SC trastuzumab (600 mg) q3w alone. All participants will be followed up for 24 months after the last participant has received the last dose of study treatment, or earlier in case of withdrawal from the study, loss to follow-up or death.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Doxorubicin Drug: Docetaxel Drug: Paclitaxel Drug: Trastuzumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: National Phase IIIb Prospective Two-Cohort Non-Randomized, Multi-centre, Open Label Study to Assess the Safety of Subcutaneous Trastuzumab and Molecular Biomarkers in Patients With Early and Locally Advanced HER2-Positive Breast Cancer
Actual Study Start Date : November 15, 2013
Actual Primary Completion Date : April 5, 2016
Actual Study Completion Date : March 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
Experimental: Trastuzumab (Vial)
Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
Drug: Doxorubicin
Participants will receive doxorubicin in doses according to the locally-approved regimen q3w (1 cycle), for 4 cycles prior to initiation of trastuzumab treatment.

Drug: Docetaxel
Participants will receive docetaxel in doses according to the locally-approved regimen q3w for 12 weeks, in combination with trastuzumab.

Drug: Paclitaxel
Participants will receive paclitaxel in doses according to the locally-approved regimen weekly for 12 weeks, in combination with trastuzumab.

Drug: Trastuzumab
Participants will receive trastuzumab 600 mg SC (vial or SID) q3w for 18 cycles.
Other Name: Herceptin

Experimental: Trastuzumab (SID)
Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy [consisting of doxorubicin, paclitaxel or docetaxel] and 14 cycles administered alone).
Drug: Doxorubicin
Participants will receive doxorubicin in doses according to the locally-approved regimen q3w (1 cycle), for 4 cycles prior to initiation of trastuzumab treatment.

Drug: Docetaxel
Participants will receive docetaxel in doses according to the locally-approved regimen q3w for 12 weeks, in combination with trastuzumab.

Drug: Paclitaxel
Participants will receive paclitaxel in doses according to the locally-approved regimen weekly for 12 weeks, in combination with trastuzumab.

Drug: Trastuzumab
Participants will receive trastuzumab 600 mg SC (vial or SID) q3w for 18 cycles.
Other Name: Herceptin




Primary Outcome Measures :
  1. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to 28 days after last dose of trastuzumab (assessed up to cut off date 05 April 2016; up to approximately 1 year) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the AEs occurring from starting on the day of or after first administration of trastuzumab and within 28 days after last dose of trastuzumab. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.


Secondary Outcome Measures :
  1. Actual Dose of Trastuzumab Administered [ Time Frame: Day 1 up last dose of trastuzumab (assessed up to cut off date 05 April 2016; up to approximately 1 year) ]
    Actual dose (mg) administered = (sum over all cycles of actual dose received [mg] divided by number of cycles). Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  2. Duration of Treatment With Trastuzumab [ Time Frame: Day 1 up last dose of trastuzumab (assessed up to cut off date 05 April 2016; up to approximately 1 year) ]
    Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  3. Percentage of Participants Who Received Concomitant Medications [ Time Frame: Screening (Day -28 to -1) up to 2.5 years (assessed up to cut off date 05 April 2016) ]
  4. Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography [ Time Frame: Day 1 up to 24 weeks ]
    In the neoadjuvant setting, the activity of two sequential drug regimens, doxorubicin-containing chemotherapy followed by paclitaxel or docetaxel chemotherapy in combination with trastuzumab, was assessed as the percentage of participants with pCR in breast and nodes using mammography. pCR was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after preoperative treatment. Data for this outcome measure were analyzed and reported only for neoadjuvant groups within each treatment arm.

  5. Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography [ Time Frame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first) (assessed up to cut off date 05 April 2016; up to approximately 2.5 years) ]
    A participant was considered as disease free if the participant was free from local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Percentage of participants with event at the cut off date were reported. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  6. Disease-Free Survival (DFS) Using Mammography [ Time Frame: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first) (assessed up to cut off date 05 April 2016; up to approximately 2.5 years) ]
    DFS was defined as the time from the first treatment to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Kaplan-Meier estimates were used for analysis. Participants who were disease-free were censored at the data cut off date. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  7. Percentage of Participants Who Died [ Time Frame: Day 1 up to death due to any cause (assessed up to cut off date 05 April 2016; up to approximately 2.5 years) ]
    Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  8. Overall Survival (OS) [ Time Frame: Day 1 up to death due to any cause (assessed up to cut off date 05 April 2016; up to approximately 2.5 years) ]
    Overall survival was defined as the time from the first treatment to death from any cause. Kaplan-Meier estimates were used for analysis. Participants who did not die were censored on the date they were last known to be alive. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm.

  9. Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ) [ Time Frame: After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year) ]
    Participants were asked the following 5 questions: (1) "Following the first injection given by the physician/nurse and training on how to use the SID, I felt comfortable injecting the study drug by myself"; (2) "The SID was convenient and easy to use"; (3) "I am confident giving myself an injection in the thigh with the SID"; (4) "Taking all things into account, I find self-administration using the SID satisfactory"; (5) "If given the opportunity, I would choose to continue self-injecting the study drug using the SID at home". Response to each question was recorded as either of the following options: "Unknown", "Strongly Disagree", "Disagree", "Unsure", "Agree", "Strongly Agree". Percentage of participants who provided responses to above questions was reported. Data for this outcome measure were analyzed and reported only for Trastuzumab (SID) arm.

  10. Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ) [ Time Frame: After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year) ]
    Percentage of HCPs providing responses to various questions related to overall ease of study drug administration was reported in different categories, where categories indicate all possible responses to such questions.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast. Stage of disease: T1-4 (T describes size of tumour from 1 to 4), N0-3 (N describes nearby lymph nodes), M0 (M describes distant metastasis)
  • HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 55 percent (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC
  • Intact skin at site of SC injection on the thigh

Exclusion Criteria:

  • History of other malignancy, except for participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies, other than breast cancer, who have been disease-free for at least 5 years
  • Severe dyspnea at rest or requiring supplementary oxygen therapy
  • 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 trastuzumab, specifically: 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), diagnosed poorly controlled hypertension
  • Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Pregnant or lactating women
  • Concurrent enrolment 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 the adhesive of the SC device (for Cohort B), or a history of severe allergic or immunological reactions, for example, difficulty to control asthma
  • Inadequate bone marrow, hepatic or renal function
  • Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with adjuvant trastuzumab SC)
  • Pre-existing motor or sensory neuropathy of Grade greater than (>) 1
  • Synchronous bilateral invasive breast cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01940497


  Show 59 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] May 27, 2014
Statistical Analysis Plan  [PDF] July 30, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01940497     History of Changes
Other Study ID Numbers: ML28879
2013-001161-16 ( EudraCT Number )
First Posted: September 12, 2013    Key Record Dates
Results First Posted: July 2, 2017
Last Update Posted: April 10, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological