SafeHer

Tahapan Penelitian : Awal
Sponsor:
Mitra Pelaksana:
Cipto Mangunkusumo Hospital; Hasan Sadikin Hospital; Sardjito Hospital; Soetomo Hospital; Dharmais National Cancer Hospital
No Registry
INA-P0Q2OY0
Tanggal Input Registry : 14-09-2017

27-06-2012
The primary objective of this study is to assess the overall safety and tolerability of trastuzumab subcutaneous (SC) in HER2-positive early breast cancer (EBC) patients with assisted administration using a conventional syringe and needle (vial formulation) or with assisted- and self-administration using a single-use injection device (SID) in selected patients.
Secondary objectives include the evaluation of the following parameters: • Efficacy (both cohorts): • Disease-free survival (DFS) • Overall survival (OS) • Patient satisfaction with trastuzumab SC administration using the SID (patients in Cohort B who went on to self-administration of the study drug). Exploratory Objectives Additional, exploratory objectives will be investigated in a subset of patients (Cohort B) at selected study sites: • To assess the immunogenicity of trastuzumab and recombinant human hyaluronidase (rHuPH20) • To examine and characterize tolerability of the trastuzumab SC over a 6 hour time period after the start of the first administration and over a 2 hour time period after the start of subsequent trastuzumab administrations (only in patients using the SID Cohort B]) • Monitoring of SID usability in a subgroup of 48 patients in Cohort B
 
SafeHer
A PHASE III PROSPECTIVE, TWO-COHORT NON-RANDOMIZED, MULTICENTER, MULTINATIONAL, OPEN-LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED- AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS THERAPY IN PATIENTS WITH OPERABLE HER2-POSITIVE EARLY BREAST CANCER
Observasional
Eligible patients with HER2-positive EBC will be allocated to one of the two following cohorts at the investigator’s discretion: • Cohort A (approximately 1800 patients): trastuzumab SC 600 mg via assisted administration into the thigh over a period of approximately 5 minutes using handheld syringes with hypodermic needles • Cohort B (approximately 700 patients): trastuzumab SC 600 mg, first assisted, then self-administered into the thigh over a period of approximately 5 minutes using the SID. For enrollment into Cohort B, patients need to be willing to self-administer the study drug from the SID based on personal instructions/training provided by an HCP during the first assisted administration in addition to a quick reference guide and an instructional animation describing the injection device handling and use, including how to respond if the SID loses sufficient contact with the body.
1800
 

Inclusion Criteria:

1. Signed written informed consent approved by the reviewing independent Ethics Committee (EC) 2. Female or male aged 18 years or above 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. 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 (T1, N0, M0) to IIIC (any T, N3, M0) that is eligible for treatment with trastuzumab Note: Patients treated without neoadjuvant or adjuvant chemotherapy, such as patients with low-risk node-negative tumors ≤ 1.0 cm, elderly patients (> 65 years of age), or patients with HER2-positive EBC but denying chemotherapy, will also be eligible to participate in the study, but their enrollment will be limited to approximately ≤ 10% of the total study population. 5. HER2-positive EBC, defined as IHC 3+ or positive in situ hybridization (ISH testing) by validated and approved methods within a certified laboratory 6. Screening left ventricular ejection fraction (LVEF) ≥ 55% as measured by echocardiography, multi-gated acquisition (MUGA) scan, or Magnetic Resonance Imaging (MRI) per local practice 7. Agreement to use an adequate, nonhormonal means of contraception by women of childbearing potential (defined as premenopausal and not surgically sterilized or < 1 year after the onset of menopause) and by male participants with partners of childbearing potential only. Examples of adequate contraceptive measures are an intrauterine device, a barrier method (condoms or diaphragm) in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not acceptable for females participating in the study. 8. Intact skin at site of SC injection on the thigh

Exclusion Criteria:

Cancer-Related Criteria 1. Previous neoadjuvant or adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent 2. History of other malignancy which could affect compliance with the protocol or interpretation of results (including previous invasive ipsilateral or contralateral breast cancer). Patients with curatively-treated carcinoma in situ of the cervix or basal cell carcinoma and patients with other curatively-treated malignancies other than breast cancer who have been disease-free for at least 5 years are eligible. 3. Past history of ductal carcinoma in situ (DCIS) within the last 5 years that has been treated with any systemic therapy OR with radiation therapy to the ipsilateral breast where invasive cancer subsequently develops. Patients who had their DCIS treated with surgery only are allowed to enter the study. 4. Metastatic disease Hematological, Biochemical, and Organ Function 5. Inadequate bone marrow function (as indicated by any of the following): • Total white blood cell count (WBC) < 2500/mm3 (< 2.5 × 109/L) • Neutrophil count < 1500/mm3 (< 1.5 × 109/L) • Platelets < 100,000/mm3 (< 100 × 109/L) • Hemoglobin < 10 g/dL 6. Impaired hepatic function (as indicated by any of the following): • Serum total bilirubin > 1.5 × upper limit of normal (ULN) • Alanine amino transferase (ALT) > 2.5 × ULN • Aspartate amino transferase (AST) > 2.5 × ULN • Alkaline phosphatase (ALP) > 2.5 × ULN 7. Impaired renal function, as indicated by serum creatinine > 1.5 × ULN Other Study Drug-Related Exclusion Criteria 8. Serious cardiac illness or medical conditions including but not confined to: • History of documented heart failure or systolic dysfunction (LVEF < 50%) • High-risk uncontrolled arrhythmias such as atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia), or higher-grade atrioventricular (AV) block (second-degree AV block Type 2 [Mobitz 2] or third-degree AV block) • Angina pectoris requiring anti-anginal medication • Clinically significant valvular heart disease • Evidence of transmural infarction on electrocardiogram (ECG) • Poorly controlled or uncontrolled hypertension (blood pressure consistently over 140/90 mmHg, despite treatment) or history of hypertensive crisis or hypertensive encephalopathy 9. Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness 10. Prior maximum cumulative dose of doxorubicin > 360 mg/m2 or maximum cumulative dose of epirubicin > 720 mg/m2 or equivalent 11. Known hypersensitivity to trastuzumab, murine proteins, or excipients, or a general hypersensitivity to adhesives (Cohort B only) 12. History of severe allergic or immunological reactions, for example, difficult to control asthma. General Exclusion Criteria 13. Pregnancy or lactation 14. Unable or unwilling to comply with the requirements of the protocol, as assessed by the investigator 15. 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 16. Major surgical procedure or significant traumatic injury within 14 days prior to the first dose of study treatment or anticipated need for major surgery during the course of study treatment except for breast cancer surgery for patient receiving study drug in the neoadjuvant setting. Patients must be free of any clinically significant sequelae of prior surgery before they can receive their first dose of study treatment. 17. More than 12 weeks between the end of the last chemotherapy cycle and the first dose of study treatment, in case these treatments are initiated sequentially. This criterion does not apply to patients who are starting trastuzumab SC without previous or concurrent chemotherapy or concurrently with chemotherapy. 18. Current peripheral neuropathy of Grade 3 or greater per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0
 
107/PT02.FK/ETIK/2012 dated 20 March 2012; 107/PT02.FK/ETIK/2012 dated 20 March 2012; KE/FK/168/EC dated 14 March 2012; 226/Panke.KKE/IX/2012; 054/PEP/04/2012 dated 27 September 2012
NA
PN.01.06.1.31.05.12.3426 dated 31 May 2012; PN.01.06.1.31.05.12.3425 dated 31 May 2012; PN.01.06.1.31.05.12.3424 dated 31 May 2012; PN.01.06.1.31.11.12.6998 dated 05 November 2012; PN.01.06.1.31.05.12.3423 dated 31 May 2012
MO28048
Djumhana Atmakusuma; Heri Fadjari; Djohan Kurnianda; Eddie Herman Tanggo; Nugroho Prayogo