A Study of Pertuzumab in Combination With Herceptin (Trastuzumab) And Vinorelbine in First Line in Patients With Metastatic or Locally Advanced HER2-Positive Breast Cancer

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565083
• Other study ID #: MO27782
• Secondary ID: 2011-003308-18
• Status: Completed
• Phase: Phase 2
• First received: March 26, 2012
• Last updated: August 24, 2016
• Start date: April 2012
• Est. completion date: October 2015

Study information

• Verified date: August 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

This two-cohort, open-label, multicenter, phase II study will assess the safety and efficacy of pertuzumab given in combination with Herceptin (trastuzumab) and vinorelbine in first line in patients with metastatic or locally advanced HER2-positive breast cancer. Patients will receive pertuzumab 840 mg and Herceptin 8 mg/kg administered sequentially as separate iv infusions on Days 1 and 2, respectively, of Cycle 1. From Cycle 2 onwards, patients will receive pertuzumab 420 mg and Herceptin 6 mg/kg, administered either sequentially as separate iv infusions on Day 1 and Day 1 or 2, respectively (Cohort 1) or together in one infusion bag on Day 1 (Cohort 2) every 3 weeks. Vinorelbine will be administered at 25 mg/m2 iv on Days 2 and 9 of Cycle 1, and at 30-35 mg/m2 on Days 1 and 8 (or Days 2 and 9) of each following 3-week cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs, or withdrawal of consent or death.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Histologically or cytologically confirmed 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 version 1.1 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 anticancer therapy in the metastatic or locally advanced 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 (NCI-CTC Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy

• Radiographic evidence of central nervous system (CNS) metastases

• Current peripheral neuropathy of Grade 3 or greater

• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma

• Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or would put the patients 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 HIV infection

• Current chronic daily treatment with corticosteroids (>/= 10 mg/day methylprednisolone or equivalent), excluding inhaled steroids

• Radiographic evidence of central nervous system (CNS) metastases that are not well controlled with continuous corticosteriod therapy.

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• pertuzumab
840 mg iv infusion Day 1 of Cycle 1, followed every 3 weeks by 420 mg iv as separate infusion on Day 1
• pertuzumab
840 mg iv infusion Day 1 of Cycle 1, followed every 3 weeks by 420 mg iv together with trastuzumab in a single infusion bag on Day 1
• trastuzumab [Herceptin]
8 mg/kg iv infusion on Day 2 of Cycle 1, followed every 3 weeks by 6 mg/kg iv as separate infusion on Day 1 or 2
• trastuzumab [Herceptin]
8 mg/kg iv infusion on Day 2 of Cycle 1, followed every 3 weeks by 6 mg/kg iv together with pertuzumab in a single infusion bag on Day 1
• vinorelbine
25 mg/m2 iv infusion on Days 2 and 9 of Cycle 1, followed by 30-35 mg/m2 on Days 1 and 8 (or Days 2 and 9) of each 3-week cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  Denmark,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rates (ORR) assessed by the investigator		approximately 3.5 years	No
Secondary	Abnormal laboratory finding		approximately 3.5 years	No
Secondary	Time to response		approximately 3.5 years	No
Secondary	Duration of response		approximately 3.5 years	No
Secondary	Progression-free survival (PFS)		approximately 3.5 years	No
Secondary	Time to progression (TTP)		approximately 3.5 years	No
Secondary	Overall survival (OS)		approximately 3.5 years	No
Secondary	Safety: Incidence of adverse events		approximately 3.5 years	No
Secondary	Cardiac safety: Incidence of congestive heart failure/change in LVEF		approximately 3.5 years	No
Secondary	Quality of life: EQ-5D/FACT-B questionnaires		approximately 3.5 years	No