Clinical trial NCT01565083: A Study to Assess Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab and Vinorelbine in Participants With Metastatic or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer
Official title: A Two-cohort, Open-label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab and Vinorelbine in First Line Patients With HER2-positive Advanced (Metastatic or Locally Advanced) Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-03-28
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This two-cohort, open-label, multicenter, phase 2 study will assess the safety and efficacy of pertuzumab given in combination with trastuzumab (Herceptin) and vinorelbine in first line participants with metastatic or locally advanced HER2-positive breast cancer. Participants will receive pertuzumab and trastuzumab administered sequentially as separate intravenous (IV) infusions (followed by vinorelbine) and conventional sequential administration of pertuzumab and trastuzumab in separate infusion bags, followed by vinorelbine.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
* HER2-positive as assessed by local laboratory on primary or metastatic tumor
* At least one measurable lesion and/or non-measurable disease evaluable according to RECIST v1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Left ventricular ejection fraction (LVEF) of at least 55%
* Life expectancy of at least 12 weeks

Exclusion Criteria:

* Previous systemic non-hormonal anti-cancer therapy in the metastatic or locally advanced breast cancer setting
* Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
* Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
* Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months
* History of persistent Grade 2 or higher (National Cancer Institute Common Terminology Criteria \[NCI-CTC\], Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy
* Radiographic evidence of central nervous system metastases that are not well controlled with local therapy (irradiation or surgery)
* Current peripheral neuropathy of NCI-CTC, version 4.0 Grade 3 or greater
* History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or cancers with a similar curative outcome as those mentioned above
* Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or would put the participants at high risk for treatment-related complications
* Inadequate hematologic, liver, or renal function
* Uncontrolled hypertension or clinically significant cardiovascular disease
* Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
* Current chronic daily treatment with corticosteroids (\>/= 10 mg/day methylprednisolone or equivalent), excluding inhaled steroids

Primary outcomes:
measure: Percentage of Participants With Best Overall Response (BOR) as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
Secondary outcomes:
measure: Time to Response as Assessed by Investigator According to RECIST v 1.1
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Duration of Response (DOR) as Assessed by Investigator According to RECIST v 1.1
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 or Death From Any Cause
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Progression-free Survival (PFS) as Assessed by Investigator According to RECIST v 1.1
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Time to Progression (TTP) as Assessed by Investigator According to RECIST v 1.1
timeFrame: Baseline, every 3 cycles up to 36 months, and every 6 cycles thereafter if progression free after 36 months, 28 days after end of treatment, every 3 months thereafter (maximum up to approximately 3.5 years)
measure: Percentage of Participants Who Died From Any Cause
timeFrame: Baseline until death (up to approximately 3.5 years)
measure: Overall Survival (OS)
timeFrame: Baseline until death (up to approximately 3.5 years)
measure: Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Visual Analogue Scale (VAS) Score
timeFrame: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire Score
timeFrame: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days)
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Stanford
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hollywood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Boston
country: United States
state: Massachusetts
city: Morristown
country: United States
state: New Jersey
city: Durham
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Fredericksburg
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Rio de Janeiro
country: Brazil
state: RJ
city: Barretos
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Herlev
country: Denmark
city: Herning
country: Denmark
city: København Ø
country: Denmark
city: Odense
country: Denmark
city: Avignon
country: France
city: Bobigny
country: France
city: Caen
country: France
city: La Tronche
country: France
city: Mont-de-marsan
country: France
city: Paris
country: France
city: Paris
country: France
city: Perigueux
country: France
city: Pierre Benite
country: France
city: Plerin
country: France
city: Rouen
country: France
city: Strasbourg
country: France
city: Tours
country: France
city: Villejuif
country: France
city: Dortmund
country: Germany
city: Dresden
country: Germany
city: Frankfurt am Main
country: Germany
city: Freiburg
country: Germany
city: Georgsmarienhütte
country: Germany
city: Goslar
country: Germany
city: Gütersloh
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Kaiserslautern
country: Germany
city: Kassel
country: Germany
city: Köln
country: Germany
city: Lebach
country: Germany
city: Leer
country: Germany
city: Moers
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Neumarkt
country: Germany
city: Ravensburg
country: Germany
city: Wuerselen
country: Germany
city: Bologna
country: Italy
state: Emilia-Romagna
city: Aviano
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Cremona
country: Italy
state: Lombardia
city: Monza
country: Italy
state: Lombardia
city: Lido Di Camaiore
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Terni
country: Italy
state: Umbria
city: Negrar
country: Italy
state: Veneto
city: Oviedo
country: Spain
state: Asturias
city: Terrassa
country: Spain
state: Barcelona
city: Santander
country: Spain
state: Cantabria
city: Barbastro
country: Spain
state: Huesca
city: Palma de Mallorca
country: Spain
state: Islas Baleares
city: La Laguna
country: Spain
state: Tenerife
city: Badajoz
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Perez EA, Lopez-Vega JM, Petit T, Zamagni C, Easton V, Kamber J, Restuccia E, Andersson M. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer: VELVET Cohort 1 final results. Breast Cancer Res. 2016 Dec 13;18(1):126. doi: 10.1186/s13058-016-0773-6.