Trastuzumab; Pertuzumab for HER2-positive early breast cancer

Inclusion criteria

• {"criterion_text":"- Signed Informed Consent Form\n- Baseline LVEF ≥ 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)\n- For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective nonhormonal contraceptive method with a failure rate of < 1% per year, or two effective nonhormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of highly effective nonhormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception\n- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception\n- A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women < 12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)\n- No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment\n- Age ≥ 18 years at time of signing Informed Consent Form\n- Ability to comply with the study protocol, in the investigator’s judgment\n- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1\n- Female and male patients with locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed node positive invasive breast cancer with initial diagnosis TNM staging any T (except T0) plus N+ and M0\n- Completed neoadjuvant treatment with pertuzumab and trastuzumab in combination with chemotherapy according to routine clinical practice, and have undergone surgery for their breast cancer. Note that study treatment cannot be initiated within < 2 weeks from surgery but must be initiated ≤ 8 weeks from surgery\n- Confirmed tpCR (total pathologic complete response), defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/is ypN0), according to local pathologist assessment\n- HER2-positive breast cancer confirmed by a local laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by IHC and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥ 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies\n- Hormone receptor status of the primary tumour determined by local assessment. Hormone receptor status may be either positive (i.e. ER-positive and/or PgR positive) or negative (i.e. ER-negative and PgR-negative)"}

Exclusion criteria

• {"criterion_text":"- Stage IV (metastatic) breast cancer\n- Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy. ● Patients with clinically negative axilla (by physical examination and radiographic imaging) may undergo a core or needle biopsy procedure prior to neoadjuvant systemic therapy if in keeping with local practice\n- Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy\n- Treatment with any investigational drug within 28 days prior to randomization\n- Serious cardiac illness or medical conditions including, but not confined to, the following: ● History of NCI CTCAE (v5) Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II ● High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block) ● Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality ● Angina pectoris requiring anti-anginal medication ● Clinically significant valvular heart disease ● Evidence of transmural infarction on ECG ● Evidence of myocardial infarction within 12 months prior to starting neoadjuvant treatment ● Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mmHg)\n- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome\n- Cumulative prior anthracycline exposure to > 360 mg/m2 of doxorubicin or its equivalent\n- Inadequate bone marrow function, defined as: ● Absolute neutrophil count < 1.5 x 109/L ● Platelet count < 100 x 109/L ● Hemoglobin < 9 g/dL\n- Impaired liver function, defined as: ● Serum (total) bilirubin > 1.25 x upper limit of normal (ULN). In case of Gilbert’s syndrome: a total bilirubin of 2 x ULN is permitted. ● Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.25 x ULN ● Albumin < 25 g/L\n- Inadequate renal function with serum creatinine > 1.5 x ULN\n- Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders)\n- Any amount of residual disease in both breast and residual nodes, other than ypT0/is ypN0, will not be allowed to enter the study\n- Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy ● Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug\n- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study\n- Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis\n- Concurrent, serious, uncontrolled infections, or known infection with HIV\n- Known hypersensitivity to study drugs, excipients, and/or murine proteins\n- Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent excluding inhaled steroids)\n- Neoadjuvant treatment with trastuzumab alone\n- Already started systemic anti-HER2 treatment for their breast cancer in the adjuvant setting\n- Need for chemotherapy during the adjuvant setting\n- Current or prior history of active malignancy (other than current breast cancer) within the last five years. Appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin or 3) stage I uterine cancer within the last five years are allowed. A patient with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years\n- Patients who have a past history of ductal carcinoma in situ (DCIS), infiltrative ductal carcinoma (IDC), lobular carcinoma in situ (LCIS) or infiltrative lobular carcinoma (ILC) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast\n- Patients with bilateral breast cancer\n- Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes"}

Primary endpoints

• {"endpoint_text":"- Average HCP time per patient per visit (per treatment cycle), measured for cycles 2-7 in the adjuvant setting, for the different administration route processes, time disaggregated per pre-specified task as well as per HCP (oncologist, nurse pharmacist and other): IV administration route process and SC administration route process include such tasks as: preparation times and administration times","definition_or_measurement_approach":"Measured for cycles 2-7 in the adjuvant setting; time disaggregated per pre-specified task and per HCP (oncologist, nurse, pharmacist and other). Includes preparation times and administration times for IV and SC processes."}
• {"endpoint_text":"- Average patient time per visit (per treatment cycle), measured for cycles 2-7 in the adjuvant setting, for the different administration route processes: patient chair time (measured as time between sitting and rising from infusion chair) and treatment room time (measured as time between entrance and exit from the treatment room)","definition_or_measurement_approach":"Measured for cycles 2-7 in the adjuvant setting. Patient chair time measured as time between sitting and rising from infusion chair; treatment room time measured as time between entrance and exit from the treatment room."}

Secondary endpoints

• {"endpoint_text":"- Average patient hospital time per visit (per treatment cycle), measured for cycles 2-7 in the adjuvant setting, for the different administration route processes measured as time between first entry and last exit from the hospital for their adjuvant treatment","definition_or_measurement_approach":"Measured for cycles 2-7 in the adjuvant setting as time between first entry and last exit from the hospital for adjuvant treatment."}
• {"endpoint_text":"- Average quantity for each consumable used per patient visit (per treatment cycle), measured for cycles 2-7 in the adjuvant setting, per pre-specified task for the different administration route processes. Milligrams wasted from partly-used vials per patient visit (per treatment cycle), measured for cycles 2-7 in the adjuvant setting","definition_or_measurement_approach":"Measured for cycles 2-7 per pre-specified task; includes average quantity of each consumable and milligrams wasted from partly-used vials per patient visit."}
• {"endpoint_text":"- To describe the safety and tolerability of PH FDC SC, P IV + H IV and P IV + H SC based on the following endpoints: o Incidence, nature and severity of all AEs, ≥ Grade 3 AEs, SAEs and cardiac AEs (including left ventricular ejection fraction [LVEF] events). o Incidence of premature withdrawal from study treatment. o Targeted vital signs and physical findings. o Targeted clinical laboratory test results.","definition_or_measurement_approach":"Safety/tolerability described by incidence, nature and severity of AEs (including ≥ Grade 3, SAEs, cardiac AEs including LVEF events), incidence of premature withdrawal, targeted vital signs/physical findings, and targeted lab results over the adjuvant treatment period."}

Spain

Latest Decision Or Authorization Date

11-01-2024

Number Of Sites

10

Number Of Participants

34

Primary sponsor

Full Name

Roche Farma S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Linical Spain S.L.

Responsibilities

Sponsor/third-party duties (codes: 10,11,6); contact: heike.duerr@linical.com

Third parties

• {"country":"Spain","full_name":"Linical Spain S.L.","duties_or_roles":"Sponsor duties codes: 10, 11, 6","organisation_type":"Pharmaceutical company"}