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

NCT01565083 | Completed Phase 2 Results

• 2 other identifiers: MO277822011-003308-18
• Study Type: interventional
• Target: 213
• Locations: 7 countries
• Sites: 80

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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)

  Tumor response was assessed by investigator according to RECIST v1.1. BOR was defined as percentage of participants with a confirmed complete response (CR) or partial response (PR). All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total or pathological nodes (with short axis \[SA\] of at least (\>/=) 15 millimeter \[mm\]) were identified as target lesions (TLs) and measured and recorded at baseline. A sum of diameters (longest for non-nodal lesions, SA for nodal lesions) for all TLs was calculated and reported as baseline sum of diameters (SD). All other lesions (or sites of disease) were identified as non-TLs. CR: disappearance of all TLs and SA reduction to less than (\<) 10 mm for nodal TLs/ non-TLs. PR: \>/=30 percent (%) decrease in SD of TLs, taking as reference baseline SD. Confirmation of response at 2 consecutive tumor assessments \>/=4 weeks apart was required. The 95% confidence interval (CI) was computed using Clopper-Pearson approach.

  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 (10)

• Time to Response as Assessed by Investigator According to RECIST v 1.1

  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)

• Duration of Response (DOR) as Assessed by Investigator According to RECIST v 1.1

  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)

• Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 or Death From Any Cause

  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)

• Progression-free Survival (PFS) as Assessed by Investigator According to RECIST v 1.1

  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)

• Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1

  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)

Study Arms (2)

Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion

EXPERIMENTAL

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).

Drug: Pertuzumab; Drug: Trastuzumab; Drug: Vinorelbine

Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion

EXPERIMENTAL

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).

Drug: Pertuzumab; Drug: Trastuzumab; Drug: Vinorelbine

Interventions

Pertuzumab DRUG

Loading dose of 840 mg on Day 1 of first 21-day cycle, followed by 420 mg on Day 1 of each subsequent cycle.

Also known as: Perjeta

Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion; Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion

Trastuzumab DRUG

Loading dose of 8 mg/kg on Day 1 of first 21-day cycle, followed by 6 mg/kg on Day 1 or 2 of each subsequent cycle.

Also known as: Herceptin

Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion; Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion

Vinorelbine DRUG

A dose of 25 mg/m\^2 followed by 30-35 mg/m\^2 on Days 2 and 9 of the first 21-day cycle and on Days 1 and 8 (or Days 2 and 9) of each subsequent cycle.

Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion; Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (80)

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Tucson, Arizona, 85724, United States

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Stanford, California, 94305-5151, United States

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Denver, Colorado, 80220, United States

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Hollywood, Florida, 33021, United States

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Miami, Florida, 33136, United States

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Plantation, Florida, 33324, United States

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Marietta, Georgia, 30060, United States

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Boston, Massachusetts, 02215, United States

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Morristown, New Jersey, 07960, United States

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Durham, North Carolina, 27710, United States

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Columbus, Ohio, 43210, United States

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Houston, Texas, 77090, United States

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San Antonio, Texas, 78229, United States

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Ogden, Utah, 84403, United States

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Fredericksburg, Virginia, 22408, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98195, United States

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Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

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Barretos, São Paulo, 14784-400, Brazil

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São Paulo, São Paulo, 01308-050, Brazil

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São Paulo, São Paulo, 01317-000, Brazil

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São Paulo, São Paulo, 04039-901, Brazil

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Herlev, 2730, Denmark

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Herning, 7400, Denmark

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København Ø, 2100, Denmark

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Odense, 5000, Denmark

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Avignon, 84082, France

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Bobigny, 93009, France

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Caen, 14076, France

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La Tronche, 38700, France

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Mont-de-Marsan, 40024, France

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Paris, 75651, France

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Paris, 75908, France

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Périgueux, 24000, France

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Pierre-Bénite, 69495, France

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Plérin, 22190, France

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Rouen, 76038, France

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Strasbourg, 67065, France

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Tours, 37044, France

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Villejuif, 94805, France

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Cologne, 50677, Germany

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Dortmund, 44263, Germany

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Dresden, 01307, Germany

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Frankfurt am Main, 60389, Germany

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Freiburg im Breisgau, 79110, Germany

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Georgsmarienhütte, 49124, Germany

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Goslar, 38642, Germany

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Gütersloh, 33332, Germany

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Hamburg, 20357, Germany

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Heidelberg, 69115, Germany

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Kaiserslautern, 67655, Germany

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Kassel, 34119, Germany

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Lebach, 66822, Germany

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Leer, 26789, Germany

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Moers, 47441, Germany

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München, 80335, Germany

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München, 80639, Germany

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Neumarkt, 92318, Germany

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Ravensburg, 88212, Germany

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Würselen, 52146, Germany

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Bologna, Emilia-Romagna, 40138, Italy

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Aviano, Friuli Venezia Giulia, 33081, Italy

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Rome, Lazio, 00189, Italy

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Genoa, Liguria, 16132, Italy

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Cremona, Lombardy, 26100, Italy

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Monza, Lombardy, 20900, Italy

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Lido di Camaiore, Tuscany, 55043, Italy

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Pisa, Tuscany, 56100, Italy

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Terni, Umbria, 05100, Italy

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Negrar, Veneto, 37024, Italy

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Badajoz, Badajoz, 06080, Spain

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Palma de Mallorca, Balearic Islands, 07198, Spain

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Terrassa, Barcelona, 08227, Spain

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Santander, Cantabria, 39008, Spain

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Barbastro, Huesca, 22300, Spain

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Madrid, Madrid, 28223, Spain

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Málaga, Malaga, 29010, Spain

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Oviedo, Principality of Asturias, 33006, Spain

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San Cristóbal de La Laguna, Tenerife, 38320, Spain

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Valencia, Valencia, 46014, Spain

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Related Publications (1)

• 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.

  PMID: 27955684 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2012
• First Posted: March 28, 2012
• Study Start: April 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 22, 2016
• Results First Posted: November 22, 2016

Record last verified: 2016-09

Locations

FR (14); IT (10); ES (10); DK (4); US (17); DE (20); BR (5)