A Study to Compare Pertuzumab + Trastuzumab + Vinorelbine vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer

iOMEDICO AG

Overview

This is a randomized, open-label, two-arm, phase III trial in Germany to investigate whether vinorelbine-based triple combination presents a less toxic treatment option than docetaxel-based triple combination in patients with HER2-positive advanced breast cancer who have not previously received any systemic treatment in the metastatic setting. The primary objective of the study is to compare patient-reported quality of life in the two treatment arms. Patients will be followed-up for survival until death or end of study after at least 79 deaths occured in each arm, whatever comes first.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Conditions

Advanced Breast Cancer HER2-positive Breast Cancer

Interventions

TrastuzumabDRUG

administered as combined therapy with pertuzumab and vinorelbine or docetaxel. Trastuzumab will be administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) on day 1 of cycle 1 (1 cycle length = 21 days), and 6 mg/kg Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

PertuzumabDRUG

administered as combined therapy with Kanjinti® and vinorelbine or docetaxel. Pertuzumab will be administered as an IV loading dose of 840 milligrams (mg) on day 1 of cycle 1 (1 cycle length = 21 days), and 420 mg Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

VinorelbineDRUG

administered as combined therapy with Kanjinti® and pertuzumab. Vinorelbine will be administered as an IV dose of 25 milligrams per kilogram (mg/kg) on days 1 and 8 of cycle 1 (1 cycle length = 21 days), and 25mg/kg up to 30 mg/kg (as per treating physician discretion) Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed and dated written informed consent prior to beginning of protocol-specific procedures. * Histologically or cytologically confirmed adenocarcinoma of the breast. Locally advanced and inoperable or metastatic disease. * HER2-positive disease, defined as IHC status HER2+++ or CISH/FISH status positive. * Female patients aged ≥ 18 years. * In case of adjuvant treatment, disease-free interval of at least 12 months after completion of adjuvant treatment (excluding hormonal therapy). * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Left Ventricular Ejection Fraction (LVEF) ≥ 50%. * For women with childbearing potential, defined as physiologically capable of becoming pregnant: * Negative pregnancy test. * Agreement to use an effective form of contraception during study treatment and for 7 months after the last dose of study treatment. * Life expectancy of at least 12 weeks. * Adequate organ and bone marrow function * Fluent in spoken and written German and willing to answer the questionnaires Exclusion Criteria: * Previous systemic treatment in palliative intention (chemotherapy, hormonal therapy and / or biological therapy) * Persistent peripheral sensory or motor neuropathy grade 2 or higher (NCI CTCAE v5.0) * Evidence of central nervous system metastases. CT or MRI of the brain is only mandatory in case of clinical suspicion of brain metastases * Current uncontrolled hypertension (systolic \> 150 mmHg and / or diastolic \> 100 mmHg) or clinically significant cardiovascular disease * History of LVEF \< 50% during or after prior (neo)adjuvant therapy with trastuzumab * Current severe, uncontrolled systemic disease (e.g. cardiovascular, pulmonary, or metabolic disease, wound healing disorder, ulcers, or bone fractures, or severe fungal, bacterial or viral infection) * Major surgery within 28 days prior to start of study medication, or anticipation of the need for major surgery during the course of study treatment * Current known infection with HIV, HBV, or HCV (testing not required) * Dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy. * Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies. * Participation in investigational studies within 30 days or five half-lives of the respective IMP, whichever is longer, prior randomization. * Pregnant or lactating women.

Locations (1)

iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Outcomes

Primary Outcomes

Patient-reported health-related quality of life (QoL): FACT-B

Area under the curve (AUC) in the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire subscale Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) after 18 weeks (irrespective of disease or treatment situation at that time point). Higher AUC indicates better quality of life. To calculate the TOI-PFB the three subscales Physical well-being (PWB - 7 statements), Functional well-being (FWB - 7 statements) and breast cancer subscale (BCS - 10 statements) are summed up. In all subscales each statement will be rated by the patient from 0 (not at all) - 4 (very much). Therefore ranges of subscales are: PWB 0 - 28; FWB 0 - 28; BCS 0 - 40; TOI-PFB 0 - 96; higher values indicate better quality of life.

Time frame: Baseline to week 18

Secondary Outcomes

Progression-free survival (PFS) assessed by the investigator

PFS is defined as time from randomization to date of progressive disease or death, whichever comes first. It will be analyzed using Kaplan-Meier method. Data will be censored at date of last contact for patients alive without progressive disease at database lock. If subsequent treatment was started prior to progressive disease, then data will be censored at the onset of this treatment.

Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)

Overall survival (OS)

OS is defined as time from randomization to date of death. It will be analyzed using Kaplan-Meier method. Data will be censored at date of last contact for patients alive at database cut/lock.

Time frame: Time from randomization to date of death (maximum up to approximately 76 months)

Overall response rate (ORR)

Overall response rate is defined as the proportion of patients achieving a complete or partial remission as best response.

Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)

Data from ClinicalTrials.gov

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DocetaxelDRUG

administered as combined therapy with Kanjinti® and pertuzumab. Docetaxel will be administered as an IV dose of 75 milligrams per square meter (mg/m\^2) on day 1 of cycle 1 (1 cycle length = 21 days), and 75 mg/m\^2 (up to 100 mg/m\^2 as per treating physician discretion) Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Clinical benefit rate (CBR)

CBR is defined as proportion of patients achieving a complete or partial remission or a stable disease lasting at least 24 weeks.

Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)

Time to treatment failure (TTF)

TTF is defined as time from randomization to discontinuation of all study medications. Date of discontinuation is the earliest end of last cycle (= 20 days after first administration of a study drug in the last cycle) OR progressive disease after last administration of any study drug OR death OR start of a subsequent treatment.

Time frame: Baseline, every 12 weeks after randomization (maximum up to 56 months)

Incidence of (Serious) Adverse events ((S)AEs)

Type, frequency and severity of adverse events (including those from the pre- and post-treatment periods) will be listed according to Common Toxicity Criteria for Adverse Events (CTCAE).