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Breast CancerPhase 1NCT01918254

A Study to Evaluate Lumretuzumab in Combination With Pertuzumab and Paclitaxel in Participants With Metastatic Breast Cancer Expressing Human Epidermal Growth Factor Receptor (HER) 3 and HER2 Protein

A Phase 1 study testing Paclitaxel, Pertuzumab and Lumretuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in 4 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 multicenter, open-label dose-escalation study with an extension phase will evaluate the safety and pharmacokinetics of lumretuzumab in combination with pertuzumab and paclitaxel in participants with metastatic breast cancer expressing HER3 and HER2 protein. 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?
Paclitaxel, Pertuzumab and Lumretuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
13 sitesin 4 countries
Study dates
6 Aug 2013to 7 Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

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 confirmed metastatic breast cancer expressing HER3 and HER2 protein
  • Participants must be willing to undergo a fresh (pretreatment) tumor/metastases biopsy that will be used to assess the level of HER3 protein expression by immunohistochemistry (IHC) and central pathology review
  • HER2 status confirmed on same tumor/metastases by a central laboratory. Breast cancer tumors and/or metastases must be HER2 IHC 1+/in-situ hybridization (ISH)- or HER2 ICH 2+/ISH- as assessed by parallel testing of protein and gene amplification using a Food and Drug Administration (FDA)-approved test
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Taxane-naive participants or participants who have received taxanes as part of an adjuvant/neoadjuvant treatment regimen with a disease-free interval of at least 1 year. Participants who have received a docetaxel-containing regimen in the metastatic setting may be eligible. Participants who have received paclitaxel/nab-paclitaxel in the metastatic setting but have discontinued paclitaxel/nab-paclitaxel for a reason other than disease progression and have had a taxane-free interval of at least 6 months may be eligible unless otherwise contraindicated at the investigator's discretion
  • Radiologically measurable or clinically evaluable disease according to RECIST criteria
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  • Last dose of systemic anti-neoplastic therapy greater than (>) 21 days prior to first study treatment infusion. Palliative radiotherapy is allowed up to 2 weeks before the first study treatment infusion
  • All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade less than or equal to (<=) 1, except alopecia (any grade)
  • Adequate hematological, liver and renal function
  • Baseline left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 50 percent (%) (measured by echocardiography)
  • Female participants of childbearing potential and male participants must agree to use effective contraception as defined by protocol during the study and for at least 6 months after the last dose of study medication
  • Participants with Gilbert's Syndrome will be eligible for the study
  • For extension Phase 2, all of the above except the inclusion criteria mentioned for taxane-naive participants or participants who have received taxanes. In addition, participants in extension Phase 2 may include:
  • Participants with no prior chemotherapy for metastatic breast cancer and/or a maximum of only one prior chemotherapy regimen in the adjuvant or neoadjuvant setting
  • Taxane-naive participants or participants who have received taxanes as a part of an adjuvant/neoadjuvant treatment regimen with a disease-free interval of at least 1 year

Who cannot join

  • History of clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic and have had no requirement for steroids or enzyme-inducing anti-convulsants in the last 14 days
  • Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including uncontrolled diabetes mellitus
  • Active or uncontrolled infections
  • Known human immunodeficiency virus (HIV) or known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Major surgery or significant traumatic injury less than (<) 28 days prior to first study treatment infusion (excluding biopsies) or anticipation of the need for a major surgery during study treatment
  • Pregnant or breast-feeding women
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  • Known hypersensitivity to any of the components of RO5479599, pertuzumab or paclitaxel
  • Participants with contraindications for paclitaxel therapy according to the Summary of Product Characteristics (SmPC)
  • Therapy with an antibody or immunotherapy concurrently or within a period of time where drug exposure is still considered biologically active (usually <5 times t1/2) prior to first dose of study treatment
  • Regular immunosuppressive therapy (that is, for organ transplantation, chronic rheumatologic disease)
  • Concurrent high doses of systemic corticosteroids (>20 milligrams [mg] of dexamethasone a day or equivalent for >7 consecutive days)
  • Baseline QTc interval of >470 milliseconds (ms), participants with baseline resting bradycardia <45 beats per minute or baseline resting tachycardia >100 beats per minute
  • Uncontrolled hypertension, unstable angina, congestive heart failure of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infraction within 6 months of enrollment or symptomatic LVEF dysfunction
  • A history of Grade >=3 peripheral neuropathy of any etiology

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Spain5 sites

  • Hospital del Mar; Servicio de Oncologia

    Barcelona, 08003

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, 28041

  • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

    Madrid, 28050

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010

Other trials in Spain

France4 sites

  • Centre Francois Baclesse; Comite Sein

    Caen, 14076

  • Institut régional du Cancer Montpellier

    Montpellier, 34298

  • Institut Curie; Oncologie Medicale

    Paris, 75231

  • Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)

    Toulouse, 31059

Other trials in France

Germany3 sites

  • Universitaetsklinikum Essen; Westdeutsches Tumorzentrum; Innere Klinik (Tumorforschung)

    Essen, 45122

  • University of Hannover; Medical School

    Hanover, 30625

  • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

    Heidelberg, 69120

Other trials in Germany

Denmark1 site

  • Rigshospitalet, Onkologisk Klinik

    København Ø, 2100

Other trials in Denmark

About this study

Official title: Phase IB, Open-Label, Multicenter, Dose-Escalation Study Followed by an Extension Phase to Evaluate the Safety, Pharmacokinetics and Activity of RO5479599, a Glycoengineered Antibody Against HER3, Administered in Combination With Pertuzumab and Paclitaxel in Patients With Metastatic Breast Cancer Expressing HER3 & HER2 Protein

This multicenter, open-label dose-escalation study with an extension phase will evaluate the safety and pharmacokinetics of lumretuzumab in combination with pertuzumab and paclitaxel in participants with metastatic breast cancer expressing HER3 and HER2 protein. Cohorts of participants will receive escalating doses of lumretuzumab intravenously (IV) every three weeks (Q3W) in combination with pertuzumab 840 milligrams (mg) IV initial dose followed by 420 mg IV Q3W and paclitaxel 80 milligrams per square meter (mg/m^2) IV weekly. After completion of dose-limiting toxicity period (21 days), the study will be conducted in two extension phase cohorts: Cohort 1 and Cohort 2. Enrollment in Extension Phase Cohort 2 will occur only upon completion of Extension Phase Cohort 1. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Conditions
Breast Cancer
Being tested
Paclitaxel, Pertuzumab, Lumretuzumab
Medical subject headings
Breast Neoplasms

What participants receive

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

  • PaclitaxelDrug

    Paclitaxel IV infusion will be administered as per schedule described in individual arm.

  • PertuzumabDrug

    Also called Perjeta

    Pertuzumab IV infusion will be administered as per schedule described in individual arm.

  • LumretuzumabDrug

    Also called RO5479599; RG7116

    Lumretuzumab will be administered as per schedule described in individual arm.

Study groups in NCT01918254
Study groupRoleWhat they receive
Lumretuzumab Dose EscalationExperimentalParticipants will receive escalating doses of lumretuzumab starting at 1000 mg IV (on Day 1, except Cycle 1 where lumretuzumab will be administered on Day 2) along with paclitaxel 80 mg/m^2 IV (on Days 1, 8, and 15), and pertuzumab 840 mg IV (on Day 1) initial dose followed by 420 mg IV, in each 21-day cycle. Participants will be treated until disease progression, unacceptable toxicities, and withdrawal from treatment for other reasons or death.
Receives: Drug: Paclitaxel; Drug: Pertuzumab; Drug: Lumretuzumab
EPC1: Lumretuzumab (Prior Chemotherapy)ExperimentalExtension phase Cohort 1 (EPC1): Participants will receive lumretuzumab 1000 mg IV (on Day 1) along with paclitaxel 80 mg/m^2 IV (on Days 1, 8, and 15), and pertuzumab 840 mg IV (on Day 1) initial dose followed by 420 mg IV, in each 21-day cycle. Participants will be treated until disease progression, unacceptable toxicities, and withdrawal from treatment for other reasons or death.
Receives: Drug: Paclitaxel; Drug: Pertuzumab; Drug: Lumretuzumab
EPC2: Lumretuzumab (Without Prior Chemotherapy)ExperimentalExtension phase Cohort 2 (EPC2): Participants will receive lumretuzumab 2000 mg IV (on Day 1) along with paclitaxel 80 mg/m^2 IV (on Days 1, 8, and 15), and pertuzumab 420 mg IV (on Day 1), in each 21-day cycle. Participants will be treated until disease progression, unacceptable toxicities, and withdrawal from treatment for other reasons or death. Only participants with no prior chemotherapy for metastatic disease and/or a maximum of only one prior chemotherapy regimen in adjuvant or neoadjuvant setting will be enrolled in this cohort.
Receives: Drug: Paclitaxel; Drug: Pertuzumab; Drug: Lumretuzumab

What is being measured

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

  1. Percentage of Participants With Dose-Limiting Toxicities (DLTs)

    Measured: Day 1 up to Day 21

  2. Percentage of Participants With Adverse Events

    Measured: Baseline up to approximately 39 months

  3. Percentage of Participants With Anti-Human Antibodies (HAHAs) to lumretuzumab [RO5479599]

    Measured: Pre-infusion (Pr-I) (0 hour [h]) on Day 1 (D1) of each Cycle (Cy) up to approximately 39 months (assessed at Pr-I on D1 of each treatment Cy up to 28 and 42-45 days after last infusion [up to approximately 39 months overall]) (1 Cy = 21 days)

  4. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 Hr) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 hours) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  5. Pharmacokinetics: Maximum Serum Concentration (Cmax) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 Hr) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 hours) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  6. Pharmacokinetics: Trough Serum Concentration (Ct) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) on D1 of each cycles beginning from Cy 2 up to 28 and 42-45 days after last infusion (up to approximately 39 months) (1 Cy = 21 days)

  7. Pharmacokinetics: Time to Reach Maximum Serum Concentration (tmax) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 Hr post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  8. Pharmacokinetics: Clearance (CL) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  9. Pharmacokinetics: Volume of distribution (V) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  10. Pharmacokinetics: Accumulation Ratio of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  11. Pharmacokinetics: Elimination Half-Life (t1/2) of lumretuzumab [RO5479599]

    Measured: Pr-I (0 h) & 3, 24, 72, 168, 264, 312, 432, & 480 h post D1 infusion (infusion duration = 1.5-2 h) of Cy4, 8 & post D2 infusion of Cy1; D1 of all other cycles up to 28 and 42-45 days after last dose (up to approximately 39 months) (1 Cy = 21 days)

  12. Pharmacokinetics: Serum Concentration at the Time of Tumor Progression (Cprog) of lumretuzumab [RO5479599]

    Measured: At the time of tumor progression (up to approximately 39 months)

  13. Pharmacokinetics: Serum Concentration at the Time of Tumor Response (Complete response [CR]/Partial Response [PR]) of lumretuzumab [RO5479599]

    Measured: At the time of tumor progression (up to approximately 39 months)

  14. Pharmacokinetics: Serum Concentration at the Time of DLT of lumretuzumab [RO5479599]

    Measured: At the time of DLT (up to 21 days)

  15. Pharmacokinetics: Serum Concentration at the Time of Tumor and Skin Biopsy (Cb) of lumretuzumab [RO5479599]

    Measured: At the time of tumor/skin biopsy (up to approximately 39 months)

  16. Pharmacokinetics: Serum Concentration at the Time of Infusion-Related Reactions (IRR) of lumretuzumab [RO5479599]

    Measured: At the time of IRR (up to approximately 39 months)

  17. Recommended Phase II Dose of lumretuzumab [RO5479599]

    Measured: Day 1 up to Day 21

Secondary outcomes (5)

  1. Percentage of Participants With Best Overall Response of CR or PR (Objective Response) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1) Criteria

    Measured: Baseline up to documented disease progression (PD) or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)

  2. Percentage of Participants With Best Overall Response of CR or PR or SD (Disease Control), Assessed Using RECIST V1.1 Criteria

    Measured: Baseline up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)

  3. Duration of Response, Assessed Using RECIST V1.1 Criteria

    Measured: From first confirmed documented objective response (CR/PR) up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)

  4. Progression-Free Survival Assessed Using RECIST V1.1 Criteria

    Measured: Baseline up to documented PD or death, whichever occurs first up to approximately 39 months (assessed at baseline thereafter every 9 weeks up to 28 days after last infusion or early discontinuation)

  5. Overall Survival

    Measured: Baseline up to death (up to approximately 39 months)

Timeline

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

  1. First posted7 Aug 2013 (estimated)
  2. Study start6 Aug 2013
  3. Primary completion7 Oct 2016
  4. Study completion7 Oct 2016

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01918254
Sponsor's protocol ID
BP28752
Other IDs
2013-000090-67
Status last verified
Sep 2017
First submitted
3 Jul 2013
Last updated
12 Sep 2017
Results posted
No

Publications

  • Schneeweiss A, Park-Simon TW, Albanell J, Lassen U, Cortes J, Dieras V, May M, Schindler C, Marme F, Cejalvo JM, Martinez-Garcia M, Gonzalez I, Lopez-Martin J, Welt A, Levy C, Joly F, Michielin F, Jacob W, Adessi C, Moisan A, Meneses-Lorente G, Racek T, James I, Ceppi M, Hasmann M, Weisser M, Cervantes A. Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer. Invest New Drugs. 2018 Oct;36(5):848-859. doi: 10.1007/s10637-018-0562-4. Epub 2018 Jan 19.

    PubMed 29349598

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Paclitaxel, Pertuzumab and Lumretuzumab in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in 4 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 15 inclusion and 14 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 12 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, France, Germany, Denmark. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 Dose-Limiting Toxicities (DLTs) (time frame: Day 1 up to Day 21). The study lists 17 primary outcomes in all. 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 NCT01918254, 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 12 Sep 2017.

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