A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (PUFFIN)
15 de novembro de 2021 atualizado por: Hoffmann-La Roche
A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab+Herceptin+Docetaxel Versus Placebo+Herceptin+Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
243
Estágio
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Beijing, China, 100142
- Beijing Cancer Hospital
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Beijing, China, 100853
- Chinese PLA General Hospital
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Beijing, China, 100021
- CHINESE ACADEMY OF MEDICAL SCIENCE; CANCER INST. & HOSPITAL; Medical ward
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Changchun, China, 130021
- The First Hospital of Jilin University
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Changzhou, China, 213003
- Changzhou First People's Hospital
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Chengdu, China, 610041
- West China Hospital, Sichuan University
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Fuzhou, China, 110016
- The 900th Hospital of PLA joint service support force
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Guangzhou, China, 510080
- Guangdong General Hospital
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Harbin, China, 150081
- Harbin Medical University Cancer Hospital
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Nanjing, China, 210029
- Jiangsu province hospital; surgery on galactophore
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Nanjing City, China, 211100
- Jiangsu Cancer Hospital
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Shanghai City, China, 200120
- Fudan University Shanghai Cancer Center
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Shenyang, China, 110042
- Liaoning Cancer Hospital & Institute
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Shenyang, China, 110001
- First Hospital of China Medical University
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Zhejiang, China, 310022
- Zhejiang Cancer Hospital
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
- HER2-positive metastatic breast cancer (MBC)
- Left ventricular ejection fraction (LVEF) greater than or equal to (>=) 55 percent (%) at baseline (within 42 days of randomization)
- Eastern Cooperative Oncology Group Performance Status of 0 or 1
- Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab)
Exclusion Criteria:
- History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
- History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
- History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (<) 12 months
- History of persistent Grade >= 2 hematologic toxicity resulting from previous adjuvant therapy
- Grade >= 3 peripheral neuropathy at randomization
- History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent
- Current clinical or radiographic evidence of central nervous system (CNS) metastases
- History of exposure to cumulative doses of anthracyclines
- Current uncontrolled hypertension or unstable angina
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, or serious cardiac arrhythmia requiring treatment
- History of myocardial infarction within 6 months of randomization
- History of LVEF decrease to < 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
- Inadequate organ function within 28 days prior to randomization
- Current severe, uncontrolled systemic disease
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- Pregnant or lactating women
- History of receiving any investigational treatment within 28 days of randomization
- Current known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or active hepatitis B virus (HBV)
- Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization
- Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
- Known hypersensitivity to any of the protocol-specified study treatments
- Concurrent participation in an interventional or noninterventional study
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador Ativo: Arm A: Placebo + Trastuzumab + Docetaxel
Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
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Docetaxel (75-mg/m^2) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Placebo matched to pertuzumab was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Outros nomes:
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Experimental: Arm B: Pertuzumab + Trastuzumab + Docetaxel
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
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Docetaxel (75-mg/m^2) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Outros nomes:
Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Prazo: From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
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Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first.
As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions.
The Kaplan-Meier approach was used to estimate median PFS for each treatment arm.
Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day).
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From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
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Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1
Prazo: At 1, 2, and 3 years
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Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first.
As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions.
The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years.
Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day).
At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3]
weeks vs. 174.79
[0.9-226.1]
weeks.
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At 1, 2, and 3 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Overall Survival
Prazo: From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
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Overall survival (OS) was defined as the time from randomization to death from any cause.
The Kaplan-Meier approach was used to estimate median OS for each treatment arm.
Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive.
Participants with no post-baseline information were censored at the time of randomization plus 1 day.
The results reported here are from the final analysis.
At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported.
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From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
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Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years
Prazo: At 1, 2, and 3 Years
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Overall survival (OS) was defined as the time from randomization to death from any cause.
The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS (i.e., alive) at 1, 2, and 3 years.
Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive.
Participants with no post-baseline information were censored at the time of randomization plus 1 day.
At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3]
weeks vs. 174.79
[0.9-226.1]
weeks.
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At 1, 2, and 3 Years
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Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1
Prazo: At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
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An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1.
As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.
Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions.
The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant.
Participants without a post-baseline tumor assessment were considered non-responders.
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At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
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Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1
Prazo: From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
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Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first.
As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.
The Kaplan-Meier approach was used to estimate median duration of objective response.
Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day).
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From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
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Number of Participants With at Least One Adverse Event
Prazo: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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The number of participants per treatment arm experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here.
Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab.
At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
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From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Number of Participants With at Least One Grade ≥3 Adverse Event
Prazo: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death.
Severe and serious are not synonymous.
Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE.
AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab.
At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
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From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment
Prazo: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab.
At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
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From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
Prazo: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm.
Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for "heart failure") and the New York Heart Association (NYHA) classification.
At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
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From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan
Prazo: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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An asymptomatic decline in LVEF event is reported as an adverse event of "ejection fraction decreased" and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab.
At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks.
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From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
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Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans
Prazo: Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years
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Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction.
LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study.
The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method was to be used throughout the study, to the extent possible.
The LVEF abnormality status categories, as a change relative to LVEF at baseline, included: Increase or no change in LVEF; Decrease of <10 LVEF points; Absolute LVEF value ≥50% and a decrease of ≥10 LVEF points; and Absolute LVEF value <50% and a decrease of ≥10 LVEF points.
The overall worst LVEF value was defined as the lowest post-baseline value up to the end of the study, including unscheduled assessments and the post-treatment period.
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Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years
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Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study
Prazo: Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months)
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The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here.
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction.
LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study.
The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible.
At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3]
weeks vs. 174.79
[0.9-226.1]
weeks.
|
Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months)
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
13 de setembro de 2016
Conclusão Primária (Real)
27 de junho de 2018
Conclusão do estudo (Real)
22 de janeiro de 2021
Datas de inscrição no estudo
Enviado pela primeira vez
7 de setembro de 2016
Enviado pela primeira vez que atendeu aos critérios de CQ
7 de setembro de 2016
Primeira postagem (Estimativa)
12 de setembro de 2016
Atualizações de registro de estudo
Última Atualização Postada (Real)
16 de dezembro de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
15 de novembro de 2021
Última verificação
1 de novembro de 2021
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- YO29296
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
produto fabricado e exportado dos EUA
Sim
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