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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01565083
First received: March 26, 2012
Last updated: September 30, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Breast Cancer
Drug: Pertuzumab
Drug: Trastuzumab
Drug: Vinorelbine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Response as Assessed by Investigator According to RECIST v 1.1 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    For participants with a BOR of CR or PR, time to response = (Date of first confirmed CR/PR - Date of first study treatment) + 1. For participants without a CR or PR, time to response = (Date of adequate last tumor assessment - Date of first study treatment) + 1. For participant with no tumor assessment (or if all assessments were progressive disease [PD]) the censoring day was set to date of first study treatment +1. CR: the disappearance of all TLs and SA reduction to <10 mm for nodal TLs/ non-TLs. PR: >/=30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at 2 consecutive tumor assessments >/=4 weeks apart was required. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. The 95% CI was computed using log-log transformation.

  • Duration of Response (DOR) as Assessed by Investigator According to RECIST v 1.1 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    DOR, in participants with a BOR of CR or PR, was defined as the period from the date of initial PR or CR until the date of PD or death from any cause. Participants with no documented PD or death after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively (regardless of the response at intermediate assessments). CR: the disappearance of all TLs and SA reduction to <10 mm for nodal TLs/ non-TLs. PR: >/=30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at 2 consecutive tumor assessments >/=4 weeks apart was required. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. The 95% CI was computed using log-log transformation.

  • Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 or Death From Any Cause [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Percentage of participants with radio-graphically documented PD as assessed by investigator according to RECIST v1.1 or death due to any cause was reported.

  • Progression-free Survival (PFS) as Assessed by Investigator According to RECIST v 1.1 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PFS was defined as the time from first intake of any study medication until the first radio-graphically documented PD as assessed by investigator according to RECIST v1.1 or death due to any cause, whichever occurred first. Participants with no PFS events were censored at the time of the last evaluable tumor assessment. Participants with no baseline or no tumor assessment after the baseline visit were censored on the date of first study treatment. PD: >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Participants who had radio-graphically documented PD as assessed by investigator according to RECIST v1.1 or died due to any cause were considered as having an event. The median PFS was estimated using Kaplan-Meier method. The 95% CI was computed using log-log transformation.

  • Percentage of Participants With Disease Progression as Assessed by Investigator According to RECIST v1.1 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Percentage of participants with radio-graphically documented PD as assessed by investigator according to RECIST v1.1 was reported.

  • Time to Progression (TTP) as Assessed by Investigator According to RECIST v 1.1 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    TTP was defined as the time from first intake of any study medication until the first radio-graphically documented PD as assessed by investigator according to RECIST v1.1. Participants who did not have a radio-graphically documented PD and had died due to reason other than PD were censored on the last available tumor assessment prior to the death date. Participants with no baseline or no tumor assessment after the baseline visit were censored on the date of first study treatment. PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. Participants who had radio-graphically documented PD as assessed by investigator according to RECIST v1.1 were considered as having an event. The median TTP was estimated using Kaplan-Meier method. The 95% CI was computed using log-log transformation.

  • Percentage of Participants Who Died From Any Cause [ Time Frame: Baseline until death (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
    Percentage of participants who died due to any cause was reported.

  • Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from first intake of any study medication to the date of death, regardless of the cause of death. Participants who were known to be alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study treatment, and participants with no post-baseline information were censored at the date of first study treatment plus 1 day. Participants who died due to any cause were considered as having an event. The median OS was estimated using Kaplan-Meier method. The 95% CI was computed using log-log transformation.

  • Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Visual Analogue Scale (VAS) Score [ Time Frame: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days) ] [ Designated as safety issue: No ]
    EQ-5D VAS: participant rated questionnaire to assess health-related quality of life (QoL) in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.

  • Change From Baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire Score [ Time Frame: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days) ] [ Designated as safety issue: No ]
    FACT-B questionnaire is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures ranges from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL.


Enrollment: 213
Study Start Date: April 2012
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pertuzumab + Trastuzumab + Vinorelbine: Separate Infusion
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
Loading dose of 840 mg on Day 1 of first 21-day cycle, followed by 420 mg on Day 1 of each subsequent cycle.
Other Name: Perjeta
Drug: Trastuzumab
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.
Other Name: Herceptin
Drug: Vinorelbine
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.
Experimental: Pertuzumab + Trastuzumab + Vinorelbine: Single Infusion
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
Loading dose of 840 mg on Day 1 of first 21-day cycle, followed by 420 mg on Day 1 of each subsequent cycle.
Other Name: Perjeta
Drug: Trastuzumab
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.
Other Name: Herceptin
Drug: Vinorelbine
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565083

  Show 80 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01565083     History of Changes
Other Study ID Numbers: MO27782  2011-003308-18 
Study First Received: March 26, 2012
Results First Received: September 30, 2016
Last Updated: September 30, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Pertuzumab
Trastuzumab
Vinblastine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016