A Study to Compare Pertuzumab + Trastuzumab + Vinorelbine vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer

NCT03811418 | Withdrawn Phase 3

• 2 other identifiers: iOM-1103832017-004749-25
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, two-arm, phase III trial in Germany to investigate whether vinorelbine-based triple combination presents a less toxic treatment option than docetaxel-based triple combination in patients with HER2-positive advanced breast cancer who have not previously received any systemic treatment in the metastatic setting. The primary objective of the study is to compare patient-reported quality of life in the two treatment arms. Patients will be followed-up for survival until death or end of study after at least 79 deaths occured in each arm, whatever comes first.

Conditions

Advanced Breast Cancer; HER2-positive Breast Cancer

Keywords

advanced breast cancer; HER2-positive; metastatic; inoperable; female; quality of life

Outcome Measures

Primary Outcomes (1)

• Patient-reported health-related quality of life (QoL): FACT-B

  Area under the curve (AUC) in the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire subscale Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) after 18 weeks (irrespective of disease or treatment situation at that time point). Higher AUC indicates better quality of life. To calculate the TOI-PFB the three subscales Physical well-being (PWB - 7 statements), Functional well-being (FWB - 7 statements) and breast cancer subscale (BCS - 10 statements) are summed up. In all subscales each statement will be rated by the patient from 0 (not at all) - 4 (very much). Therefore ranges of subscales are: PWB 0 - 28; FWB 0 - 28; BCS 0 - 40; TOI-PFB 0 - 96; higher values indicate better quality of life.

  Baseline to week 18

Secondary Outcomes (33)

• Progression-free survival (PFS) assessed by the investigator

  Baseline, every 12 weeks after randomization (maximum up to 76 months)

• Overall survival (OS)

  Time from randomization to date of death (maximum up to approximately 76 months)

• Overall response rate (ORR)

  Baseline, every 12 weeks after randomization (maximum up to 76 months)

• Clinical benefit rate (CBR)

  Baseline, every 12 weeks after randomization (maximum up to 76 months)

• Time to treatment failure (TTF)

  Baseline, every 12 weeks after randomization (maximum up to 56 months)

Study Arms (2)

Kanjinti/Pertuzumab plus Vinorelbine

EXPERIMENTAL

Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Vinorelbine

Kanjinti/Pertuzumab plus Docetaxel

ACTIVE COMPARATOR

Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel

Interventions

Trastuzumab DRUG

administered as combined therapy with pertuzumab and vinorelbine or docetaxel. Trastuzumab will be administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) on day 1 of cycle 1 (1 cycle length = 21 days), and 6 mg/kg Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Also known as: Kanjinti®, ABP 980

Kanjinti/Pertuzumab plus Docetaxel; Kanjinti/Pertuzumab plus Vinorelbine

Pertuzumab DRUG

administered as combined therapy with Kanjinti® and vinorelbine or docetaxel. Pertuzumab will be administered as an IV loading dose of 840 milligrams (mg) on day 1 of cycle 1 (1 cycle length = 21 days), and 420 mg Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Also known as: Perjeta®

Kanjinti/Pertuzumab plus Docetaxel; Kanjinti/Pertuzumab plus Vinorelbine

Vinorelbine DRUG

administered as combined therapy with Kanjinti® and pertuzumab. Vinorelbine will be administered as an IV dose of 25 milligrams per kilogram (mg/kg) on days 1 and 8 of cycle 1 (1 cycle length = 21 days), and 25mg/kg up to 30 mg/kg (as per treating physician discretion) Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Kanjinti/Pertuzumab plus Vinorelbine

Docetaxel DRUG

administered as combined therapy with Kanjinti® and pertuzumab. Docetaxel will be administered as an IV dose of 75 milligrams per square meter (mg/m\^2) on day 1 of cycle 1 (1 cycle length = 21 days), and 75 mg/m\^2 (up to 100 mg/m\^2 as per treating physician discretion) Q3W on day 1 of subsequent cycles until progressive disease, intolerable toxicity, or death.

Kanjinti/Pertuzumab plus Docetaxel

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent prior to beginning of protocol-specific procedures.
• Histologically or cytologically confirmed adenocarcinoma of the breast. Locally advanced and inoperable or metastatic disease.
• HER2-positive disease, defined as IHC status HER2+++ or CISH/FISH status positive.
• Female patients aged ≥ 18 years.
• In case of adjuvant treatment, disease-free interval of at least 12 months after completion of adjuvant treatment (excluding hormonal therapy).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• For women with childbearing potential, defined as physiologically capable of becoming pregnant:
• Negative pregnancy test.
• Agreement to use an effective form of contraception during study treatment and for 7 months after the last dose of study treatment.
• Life expectancy of at least 12 weeks.
• Adequate organ and bone marrow function
• Fluent in spoken and written German and willing to answer the questionnaires

You may not qualify if:

• Previous systemic treatment in palliative intention (chemotherapy, hormonal therapy and / or biological therapy)
• Persistent peripheral sensory or motor neuropathy grade 2 or higher (NCI CTCAE v5.0)
• Evidence of central nervous system metastases. CT or MRI of the brain is only mandatory in case of clinical suspicion of brain metastases
• Current uncontrolled hypertension (systolic \> 150 mmHg and / or diastolic \> 100 mmHg) or clinically significant cardiovascular disease
• History of LVEF \< 50% during or after prior (neo)adjuvant therapy with trastuzumab
• Current severe, uncontrolled systemic disease (e.g. cardiovascular, pulmonary, or metabolic disease, wound healing disorder, ulcers, or bone fractures, or severe fungal, bacterial or viral infection)
• Major surgery within 28 days prior to start of study medication, or anticipation of the need for major surgery during the course of study treatment
• Current known infection with HIV, HBV, or HCV (testing not required)
• Dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy.
• Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies.
• Participation in investigational studies within 30 days or five half-lives of the respective IMP, whichever is longer, prior randomization.
• Pregnant or lactating women.

Sponsors & Collaborators

• iOMEDICO AG: lead
• Arbeitsgemeinschaft fur Internistische Onkologie: collaborator
• Amgen: collaborator

Study Sites (1)

iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Related Publications (7)

• Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sorensen PG, Moller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. doi: 10.1200/JCO.2010.30.8213. Epub 2010 Dec 13.

  PMID: 21149659 BACKGROUND

• Andersson M, Lopez-Vega JM, Petit T, Zamagni C, Easton V, Kamber J, Restuccia E, Perez EA. Efficacy and Safety of Pertuzumab and Trastuzumab Administered in a Single Infusion Bag, Followed by Vinorelbine: VELVET Cohort 2 Final Results. Oncologist. 2017 Oct;22(10):1160-1168. doi: 10.1634/theoncologist.2017-0079. Epub 2017 Jun 7.

  PMID: 28592618 BACKGROUND

• Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.

  PMID: 22149875 BACKGROUND

• Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. doi: 10.1002/cncr.22885.

  PMID: 17614302 BACKGROUND

• Cortes J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. doi: 10.1093/annonc/mdt274. Epub 2013 Jul 17.

  PMID: 23868905 BACKGROUND

• 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 BACKGROUND

• Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.

  PMID: 25693012 BACKGROUND

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Trastuzumab; pertuzumab; Vinorelbine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Anja Welt, Dr.

  Essen University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: January 22, 2019
• Study Start: January 1, 2019
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: November 26, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)