Advanced Breast CancerPhase 3ATTILANCT03811418
A Study to Compare Pertuzumab + Trastuzumab + Vinorelbine vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer
A Phase 3 study testing Trastuzumab, Pertuzumab and Vinorelbine in people with Advanced Breast Cancer and HER2-positive Breast Cancer, run by iOMEDICO AG at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer, HER2-positive Breast Cancer
- What is being tested?
- Trastuzumab, Pertuzumab and Vinorelbine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2019to Apr 2019
- Phase
- Phase 3
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Study to Compare Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Vinorelbine With Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Docetaxel as First-line Treatment for HER2-positive Advanced Breast Cancer
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.
- Being tested
- Trastuzumab, Pertuzumab, Vinorelbine, Docetaxel
- Keywords
- advanced breast cancer, HER2-positive, metastatic, inoperable, female, quality of life
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Kanjinti®, ABP 980
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.
PertuzumabDrug
Also called Perjeta®
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.
VinorelbineDrug
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.
DocetaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Kanjinti/Pertuzumab plus Vinorelbine | Experimental | Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Vinorelbine |
| Kanjinti/Pertuzumab plus Docetaxel | Active comparator | Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to week 18
Secondary outcomes (33)
Progression-free survival (PFS) assessed by the investigator
PFS is defined as time from randomization to date of progressive disease or death, whichever comes first. It will be analyzed using Kaplan-Meier method. Data will be censored at date of last contact for patients alive without progressive disease at database lock. If subsequent treatment was started prior to progressive disease, then data will be censored at the onset of this treatment.
Measured: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Overall survival (OS)
OS is defined as time from randomization to date of death. It will be analyzed using Kaplan-Meier method. Data will be censored at date of last contact for patients alive at database cut/lock.
Measured: Time from randomization to date of death (maximum up to approximately 76 months)
Overall response rate (ORR)
Overall response rate is defined as the proportion of patients achieving a complete or partial remission as best response.
Measured: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Clinical benefit rate (CBR)
CBR is defined as proportion of patients achieving a complete or partial remission or a stable disease lasting at least 24 weeks.
Measured: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Time to treatment failure (TTF)
TTF is defined as time from randomization to discontinuation of all study medications. Date of discontinuation is the earliest end of last cycle (= 20 days after first administration of a study drug in the last cycle) OR progressive disease after last administration of any study drug OR death OR start of a subsequent treatment.
Measured: Baseline, every 12 weeks after randomization (maximum up to 56 months)
Incidence of (Serious) Adverse events ((S)AEs)
Type, frequency and severity of adverse events (including those from the pre- and post-treatment periods) will be listed according to Common Toxicity Criteria for Adverse Events (CTCAE).
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Hemoglobin
The amount of hemoglobin in the blood will be measured in g/dL as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Platelet Count
The number of platelets in the blood will be counted as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Leukocytes
The number of leukocytes in the blood will be counted as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Absolute Neutrophil Count
The absolute neutrophil count will be determined as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Safety monitoring (coagulation): Coagulation (INR)
Coagulation (INR) as per clinical routine will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Alkaline Phosphatase
Alkaline phosphatase will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Alanine transaminase (ALT)
ALT will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Aspartate transaminase (AST)
AST will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Bilirubin total
Total bilirubin will be measured in mg/dL as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Creatinine (Serum)
Serum creatinine will be measured in µmol/L as per clinical routine and will be displayed using by-patient listings.
Measured: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Left Ventricular Ejection Fraction (LVEF) monitoring
Incidence of clinically relevant LVEF levels. Change from baseline at each assessment time point, worst-on-treatment will be displayed using descriptive statistics.
Measured: LVEF at baseline, every three months thereafter until end of treatment, then every six months for 24 months thereafter (maximum up to 76 months)
Patient-reported health-related quality of life (QoL): Trial Outcome Index-Physical/Functional/Breast (TOI-PFB)
AUC in TOI-PFB at 12, 18, 24 and 36 months.
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 12, 18, 24 and 36 months (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.
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B TOI-PFB
Time to decline by 5 points in the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire subscale Trial Outcome Index-Physical/Functional/Breast (TOI-PFB).
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; decline of scale indicates worsening quality of life.
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B total score
Change from baseline in the FACT-B total score for all questionnaire timepoints. To calculate FACT-B total score patient ratings from 0 (not at all) - 4 (very much) to each of the 37 questionnaire statement are summed up. Total score range: 0 - 148. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale physical well-being (PWB)
Change from baseline in the FACT-B subscale PWB for all questionnaire timepoints. PWB subscale consists of 7 statements leading to a scale range of 0-28. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale social/family well-being (SWB)
Change from baseline in the FACT-B subscale SWB for all questionnaire timepoints. SWB subscale consists of 8 statements leading to a scale range of 0-32. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale emotional well-being (EWB)
Change from baseline in the FACT-B subscale EWB for all questionnaire timepoints. EWB subscale consists of 6 statements leading to a scale range of 0-24. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale functional well-being (FWB)
Change from baseline in the FACT-B subscale FWB for all questionnaire timepoints. FWB subscale consists of 7 statements leading to a scale range of 0-28. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS)
Change from baseline in the FACT-B BCS score for all questionnaire timepoints. BCS consists of 10 statements leading to a score range of 0-40. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS) score decline
Time to decline by 2 points in the FACT-B BCS score. BCS consists of 10 statements leading to a score range of 0-40. BCS score decline indicates worsening quality of life.
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT/GOG-Ntx4 subscale
Change from baseline in the FACT/GOG-Ntx4 subscale for all questionnaire timepoints. FACT/GOG-Ntx4 subscale consists of 11 statements leading to a scale range of 0-44. Higher values indicate better quality of life
Measured: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Exploratory endpoint: Treatment costs
Treatment costs (drug costs)
Measured: From randomization until end of treatment (maximum up to 56 months).
Exploratory endpoints: Duration of hospitalizations
Total duration of hospitalizations (per patients)
Measured: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Number of hospitalizations
Number of hospitalizations (in-patient stays)
Measured: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Reasons for hospitalizations
Reasons for hospitalizations
Measured: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Febrile infections
Incidence of febrile infections
Measured: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Employment status
Employment status (kind and duration of sick leaves)
Measured: From randomization until end of treatment (maximum up to 56 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study startJan 2019 (estimated)
- Primary completionApr 2019 (estimated)
- Study completionApr 2019 (estimated)
Why it stopped: Study approved with treatment regimen based on current guidelines. However, reimbursement of IMP was not feasible.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by iOMEDICO AGThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- iOMEDICO AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Arbeitsgemeinschaft fur Internistische Onkologie, Amgen
- Responsible party
- Sponsor
- Investigators
- Anja Welt, Dr., Principal investigator, Essen University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03811418
- Sponsor's protocol ID
- iOM-110383
- Other IDs
- 2017-004749-25, 2017
- Acronym
- ATTILA
- Status last verified
- Apr 2019
- First submitted
- 13 Dec 2018
- Last updated
- 26 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21149659Andersson 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.
PubMed 28592618Baselga 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.
PubMed 22149875Burstein 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.
PubMed 17614302Cortes 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.
PubMed 23868905Perez 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 27955684Swain 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.
PubMed 25693012
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study to Compare Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Vinorelbine With Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Docetaxel as First-line Treatment for HER2-positive Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT03811418
- Acronym / sponsor ID
- ATTILA / iOM-110383
- Keywords
- advanced breast cancer, HER2-positive, metastatic, inoperable, female, quality of life
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study approved with treatment regimen based on current guidelines. However, reimbursement of IMP was not feasible.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- iOMEDICO AGIndustry (pharma, biotech, devices)
- Collaborators
- Arbeitsgemeinschaft fur Internistische Onkologie, Amgen
- Study start
- Jan 2019 (estimated)
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 22 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Kanjinti/Pertuzumab plus Vinorelbine | Experimental | Drug: Trastuzumab, Drug: Pertuzumab, Drug: VinorelbinePatients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine. |
| Kanjinti/Pertuzumab plus Docetaxel | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: DocetaxelPatients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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).
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: Kanjinti®, ABP 980administered 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. | Drug | Kanjinti/Pertuzumab plus Docetaxel, Kanjinti/Pertuzumab plus Vinorelbine |
| PertuzumabAlso: Perjeta®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. | Drug | Kanjinti/Pertuzumab plus Docetaxel, Kanjinti/Pertuzumab plus Vinorelbine |
| Vinorelbineadministered 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. | Drug | Kanjinti/Pertuzumab plus Vinorelbine |
| Docetaxeladministered 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. | Drug | Kanjinti/Pertuzumab plus Docetaxel |
Primary outcome
Patient-reported health-related quality of life (QoL): FACT-B
Time frame: Baseline to week 18
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.
33 secondary outcomes
Progression-free survival (PFS) assessed by the investigator
Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Overall survival (OS)
Time frame: Time from randomization to date of death (maximum up to approximately 76 months)
Overall response rate (ORR)
Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Clinical benefit rate (CBR)
Time frame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
Time to treatment failure (TTF)
Time frame: Baseline, every 12 weeks after randomization (maximum up to 56 months)
Incidence of (Serious) Adverse events ((S)AEs)
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Hemoglobin
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Platelet Count
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Leukocytes
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Blood count: Absolute Neutrophil Count
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Safety monitoring (coagulation): Coagulation (INR)
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Alkaline Phosphatase
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Alanine transaminase (ALT)
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Aspartate transaminase (AST)
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Bilirubin total
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Clinical chemistry: Creatinine (Serum)
Time frame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Left Ventricular Ejection Fraction (LVEF) monitoring
Time frame: LVEF at baseline, every three months thereafter until end of treatment, then every six months for 24 months thereafter (maximum up to 76 months)
Patient-reported health-related quality of life (QoL): Trial Outcome Index-Physical/Functional/Breast (TOI-PFB)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B TOI-PFB
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B total score
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale physical well-being (PWB)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale social/family well-being (SWB)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale emotional well-being (EWB)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B subscale functional well-being (FWB)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS)
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS) score decline
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Patient-reported health-related quality of life (QoL): FACT/GOG-Ntx4 subscale
Time frame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
Exploratory endpoint: Treatment costs
Time frame: From randomization until end of treatment (maximum up to 56 months).
Exploratory endpoints: Duration of hospitalizations
Time frame: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Number of hospitalizations
Time frame: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Reasons for hospitalizations
Time frame: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Febrile infections
Time frame: From randomization until end of treatment (maximum up to 57 months).
Exploratory endpoints: Employment status
Time frame: From randomization until end of treatment (maximum up to 56 months).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Background: PubMed 21149659Andersson 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.
- Background: PubMed 28592618Andersson 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.
- Background: PubMed 22149875Baselga 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.
- Background: PubMed 17614302Burstein 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.
- Background: PubMed 23868905Cortes 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.
- Background: PubMed 27955684Perez 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.
- Background: PubMed 25693012Swain 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anja Welt, Dr. principal investigator
Essen University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab, Pertuzumab and Vinorelbine in people with Advanced Breast Cancer and HER2-positive Breast Cancer, run by iOMEDICO AG at 1 site in Germany.
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 13 inclusion and 12 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: withdrawn, as of the sponsor's last update on 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was withdrawn before enrolling participants, so there are no results.
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?
Patient-reported health-related quality of life (QoL): FACT-B (time frame: Baseline to week 18). 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 NCT03811418, which also lists 7 linked publications.
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 26 Nov 2019.