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 (VELVET)

Roche

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab; Drug: Vinorelbine; Drug: Pertuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01565083

MO27782

2011-003308-18 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 213 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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213 participants in 2 patient groups

Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion

Experimental group

Description:

Pertuzumab will be administered as IV infusion on Day 1 of the first treatment cycle (1 cycle = 21 days) as a loading dose of 840 milligrams (mg), followed by 420 mg on Day 1 of each subsequent cycle. Trastuzumab will be administered as IV infusion on Day 2 of the first treatment cycle as a loading dose of 8 mg per kilogram (mg/kg), followed by 6 mg/kg on Day 2 of each subsequent cycle. Vinorelbine IV infusion (will be administered after trastuzumab) on Day 2 and Day 9 of the first treatment cycle at a dose of 25 mg per meter-squared (mg/m\^2) followed by 30-35 mg/m\^2 on Day 2 and Day 9 of each subsequent cycle. Pertuzumab and trastuzumab will be administered sequentially in separate infusion bags, followed by vinorelbine until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end (up to 47 cycles).

Treatment:

Drug: Pertuzumab

Drug: Vinorelbine

Drug: Trastuzumab

Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion

Experimental group

Description:

Pertuzumab will be administered as IV infusion on Day 1 of the first treatment cycle as a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent cycle. Trastuzumab will be administered as IV infusion on Day 2 of the first treatment cycle as a loading dose of 8 mg/kg, followed by 6 mg/kg on Day 1 of each subsequent cycle. Vinorelbine IV infusion on Day 2 and Day 9 of the first treatment cycle at a dose of 25 mg/m\^2 followed by 30-35 mg/m\^2 on Day 1 and Day 8 of each subsequent cycle. If administration of all 3 drugs is well tolerated in Cycle 1, then on Day 1 of each subsequent cycle, pertuzumab 420 mg and trastuzumab 6 mg/kg will be administered in a single infusion bag, followed by vinorelbine until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end (up to 47 cycles).

Treatment:

Drug: Pertuzumab

Drug: Vinorelbine

Drug: Trastuzumab