Time and Motion Study of a Subcutaneous Fixed Dose Combination of Pertuzumab and Trastuzumab for the Treatment of Patients with HER2-POSITIVE Early Breast Cancer (Phatima)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Roche Farma S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Apr 2021 → ongoing

Decision date (initial)

2024-01-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Roche Farma S.A

External identifiers

EU CT number

2023-509321-50-00

EudraCT number

2020-004241-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

Quantify HCP time savings for PH FDC SC vs Perjeta IV + Herceptin IV and Perjeta IV + Herceptin SC in the treatment of HER2-positive EBC patients; and quantify patient time savings for PH FDC SC vs Perjeta IV + Herceptin IV and Perjeta IV + Herceptin SC.

Secondary objectives 3

1. Quantify total patient time spent in hospital for the different administration routes.
2. Quantify resource utilization reduction in terms of consumables and drug wastage related to the different administration routes.
3. To describe the safety and tolerability of PH FDC SC, P IV + H IV and P IV + H SC over the entire adjuvant treatment period.

Conditions and MedDRA coding

HER2-POSITIVE EARLY BREAST CANCER

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Signed Informed Consent Form
2. Age ≥ 18 years at time of signing Informed Consent Form
3. Ability to comply with the study protocol, in the investigator’s judgment
4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
5. 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
6. 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
7. 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
8. 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
9. 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)
10. Baseline LVEF ≥ 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
11. 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
12. 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
13. 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)
14. 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

Exclusion criteria 25

1. Stage IV (metastatic) breast cancer
2. Any amount of residual disease in both breast and residual nodes, other than ypT0/is ypN0, will not be allowed to enter the study
3. Neoadjuvant treatment with trastuzumab alone
4. Already started systemic anti-HER2 treatment for their breast cancer in the adjuvant setting
5. Need for chemotherapy during the adjuvant setting
6. 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
7. 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
8. Patients with bilateral breast cancer
9. Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
10. 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
11. Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
12. Treatment with any investigational drug within 28 days prior to randomization
13. 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)
14. 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
15. Cumulative prior anthracycline exposure to > 360 mg/m2 of doxorubicin or its equivalent
16. Inadequate bone marrow function, defined as: ● Absolute neutrophil count < 1.5 x 109/L ● Platelet count < 100 x 109/L ● Hemoglobin < 9 g/dL
17. 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
18. Inadequate renal function with serum creatinine > 1.5 x ULN
19. Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders)
20. 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
21. 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
22. Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
23. Concurrent, serious, uncontrolled infections, or known infection with HIV
24. Known hypersensitivity to study drugs, excipients, and/or murine proteins
25. Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent excluding inhaled steroids)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. 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)

Secondary endpoints 3

1. 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
2. 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
3. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Roche Farma S.A.

Sponsor organisation

Roche Farma S.A.

Address

Calle De La Ribera Del Loira 50

City

Madrid

Postcode

28042

Country

Spain

Scientific contact point

Organisation

Roche Farma S.A.

Contact name

Julian Lagunar

Public contact point

Organisation

Roche Farma S.A.

Contact name

Julian Lagunar

Third parties 1

Sponsor responsibilities

Article 77 compliance

Roche Farma S.A.

Contact point sponsor

Roche Farma S.A.

Article 77 implementation

Roche Farma S.A.

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications