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AzTrials

Breast CancerPhase 2VELVETNCT01565083

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

A Phase 2 study testing Pertuzumab, Trastuzumab and Vinorelbine in people with Breast Cancer, run by Hoffmann-La Roche at 80 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Pertuzumab, Trastuzumab and Vinorelbine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
213 participants
Where
80 sitesin 7 countries
Study dates
Apr 2012to Oct 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 13Show fewer
  • 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 locations and contacts

80 sites in 7 countries.

80 sites in 7 countries

Germany20 sites
  • Study site

    Cologne, 50677

  • Study site

    Dortmund, 44263

  • Study site

    Dresden, 01307

  • Study site

    Frankfurt am Main, 60389

  • Study site

    Freiburg im Breisgau, 79110

  • Study site

    Georgsmarienhütte, 49124

  • Study site

    Goslar, 38642

  • Study site

    Gütersloh, 33332

  • Study site

    Hamburg, 20357

  • Study site

    Heidelberg, 69115

  • Study site

    Kaiserslautern, 67655

  • Study site

    Kassel, 34119

  • Study site

    Lebach, 66822

  • Study site

    Leer, 26789

  • Study site

    Moers, 47441

  • Study site

    München, 80335

  • Study site

    München, 80639

  • Study site

    Neumarkt, 92318

  • Study site

    Ravensburg, 88212

  • Study site

    Würselen, 52146

Other trials in Germany

United States17 sites
  • Study site

    Boston, Massachusetts, 02215

  • Study site

    Columbus, Ohio, 43210

  • Study site

    Denver, Colorado, 80220

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Fredericksburg, Virginia, 22408

  • Study site

    Hollywood, Florida, 33021

  • Study site

    Houston, Texas, 77090

  • Study site

    Marietta, Georgia, 30060

  • Study site

    Miami, Florida, 33136

  • Study site

    Morristown, New Jersey, 07960

  • Study site

    Ogden, Utah, 84403

  • Study site

    Plantation, Florida, 33324

  • Study site

    San Antonio, Texas, 78229

  • Study site

    Seattle, Washington, 98101

  • Study site

    Seattle, Washington, 98195

  • Study site

    Stanford, California, 94305-5151

  • Study site

    Tucson, Arizona, 85724

Other trials in United States

France14 sites
  • Study site

    Avignon, 84082

  • Study site

    Bobigny, 93009

  • Study site

    Caen, 14076

  • Study site

    La Tronche, 38700

  • Study site

    Mont-de-Marsan, 40024

  • Study site

    Paris, 75651

  • Study site

    Paris, 75908

  • Study site

    Périgueux, 24000

  • Study site

    Pierre-Bénite, 69495

  • Study site

    Plérin, 22190

  • Study site

    Rouen, 76038

  • Study site

    Strasbourg, 67065

  • Study site

    Tours, 37044

  • Study site

    Villejuif, 94805

Other trials in France

Italy10 sites
  • Study site

    Aviano, Friuli Venezia Giulia, 33081

  • Study site

    Bologna, Emilia-Romagna, 40138

  • Study site

    Cremona, Lombardy, 26100

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Lido di Camaiore, Tuscany, 55043

  • Study site

    Monza, Lombardy, 20900

  • Study site

    Negrar, Veneto, 37024

  • Study site

    Pisa, Tuscany, 56100

  • Study site

    Rome, Lazio, 00189

  • Study site

    Terni, Umbria, 05100

Other trials in Italy

Spain10 sites
  • Study site

    Badajoz, Badajoz, 06080

  • Study site

    Barbastro, Huesca, 22300

  • Study site

    Madrid, Madrid, 28223

  • Study site

    Málaga, Malaga, 29010

  • Study site

    Oviedo, Principality of Asturias, 33006

  • Study site

    Palma de Mallorca, Balearic Islands, 07198

  • Study site

    San Cristóbal de La Laguna, Tenerife, 38320

  • Study site

    Santander, Cantabria, 39008

  • Study site

    Terrassa, Barcelona, 08227

  • Study site

    Valencia, Valencia, 46014

Other trials in Spain

Brazil5 sites
  • Study site

    Barretos, São Paulo, 14784-400

  • Study site

    Rio de Janeiro, Rio de Janeiro, 20560-120

  • Study site

    São Paulo, São Paulo, 01308-050

  • Study site

    São Paulo, São Paulo, 01317-000

  • Study site

    São Paulo, São Paulo, 04039-901

Other trials in Brazil

Denmark4 sites
  • Study site

    Herlev, 2730

  • Study site

    Herning, 7400

  • Study site

    København Ø, 2100

  • Study site

    Odense, 5000

Other trials in Denmark

About this study

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

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
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PertuzumabDrug

    Also called Perjeta

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

  • TrastuzumabDrug

    Also called Herceptin

    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.

  • VinorelbineDrug

    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.

Study groups in NCT01565083
Study groupRoleWhat they receive
Pertuzumab + Trastuzumab + Vinorelbine: Separate InfusionExperimentalPertuzumab 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).
Receives: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Vinorelbine
Pertuzumab + Trastuzumab + Vinorelbine: Single InfusionExperimentalPertuzumab 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).
Receives: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Vinorelbine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)
  1. Time to Response as Assessed by Investigator According to RECIST v 1.1

    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.

    Measured: 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)

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

    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.

    Measured: 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)

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

    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.

    Measured: 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)

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

    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.

    Measured: 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)

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

    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.

    Measured: 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)

  6. Time to Progression (TTP) as Assessed by Investigator According to RECIST v 1.1

    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.

    Measured: 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)

  7. Percentage of Participants Who Died From Any Cause

    Percentage of participants who died due to any cause was reported.

    Measured: Baseline until death (up to approximately 3.5 years)

  8. Overall Survival (OS)

    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.

    Measured: Baseline until death (up to approximately 3.5 years)

  9. Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Visual Analogue Scale (VAS) Score

    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.

    Measured: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days)

  10. Change From Baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B) Questionnaire Score

    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.

    Measured: Baseline, thereafter every 3 cycles from Cycle 3 to Cycle 45 (each cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionOct 2015
  4. Study completionOct 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
213 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01565083
Sponsor's protocol ID
MO27782
Other IDs
2011-003308-18
Acronym
VELVET
Status last verified
Sep 2016
First submitted
26 Mar 2012
Last updated
22 Nov 2016

Publications

  • 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.

    PubMed 27955684

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pertuzumab, Trastuzumab and Vinorelbine in people with Breast Cancer, run by Hoffmann-La Roche at 80 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in Germany, United States, France, Italy, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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) (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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01565083, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.

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