Clinical trial NCT03811418: A Study to Compare Pertuzumab + Trastuzumab + Vinorelbine vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Advanced Breast Cancer
HER2-positive Breast Cancer
Keywords: advanced breast cancer
HER2-positive
metastatic
inoperable
female
quality of life
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Arbeitsgemeinschaft fur Internistische Onkologie
name: Amgen
First posted: 2019-01-22
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Patient-reported health-related quality of life (QoL): FACT-B
timeFrame: Baseline to week 18
Secondary outcomes:
measure: Progression-free survival (PFS) assessed by the investigator
timeFrame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
measure: Overall survival (OS)
timeFrame: Time from randomization to date of death (maximum up to approximately 76 months)
measure: Overall response rate (ORR)
timeFrame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
measure: Clinical benefit rate (CBR)
timeFrame: Baseline, every 12 weeks after randomization (maximum up to 76 months)
measure: Time to treatment failure (TTF)
timeFrame: Baseline, every 12 weeks after randomization (maximum up to 56 months)
measure: Incidence of (Serious) Adverse events ((S)AEs)
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Blood count: Hemoglobin
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Blood count: Platelet Count
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Blood count: Leukocytes
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Blood count: Absolute Neutrophil Count
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Safety monitoring (coagulation): Coagulation (INR)
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Clinical chemistry: Alkaline Phosphatase
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Clinical chemistry: Alanine transaminase (ALT)
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Clinical chemistry: Aspartate transaminase (AST)
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Clinical chemistry: Bilirubin total
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Clinical chemistry: Creatinine (Serum)
timeFrame: From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
measure: Left Ventricular Ejection Fraction (LVEF) monitoring
timeFrame: LVEF at baseline, every three months thereafter until end of treatment, then every six months for 24 months thereafter (maximum up to 76 months)
measure: Patient-reported health-related quality of life (QoL): Trial Outcome Index-Physical/Functional/Breast (TOI-PFB)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B TOI-PFB
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B total score
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B subscale physical well-being (PWB)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B subscale social/family well-being (SWB)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B subscale emotional well-being (EWB)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B subscale functional well-being (FWB)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS)
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS) score decline
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Patient-reported health-related quality of life (QoL): FACT/GOG-Ntx4 subscale
timeFrame: Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).
measure: Exploratory endpoint: Treatment costs
timeFrame: From randomization until end of treatment (maximum up to 56 months).
measure: Exploratory endpoints: Duration of hospitalizations
timeFrame: From randomization until end of treatment (maximum up to 57 months).
measure: Exploratory endpoints: Number of hospitalizations
timeFrame: From randomization until end of treatment (maximum up to 57 months).
measure: Exploratory endpoints: Reasons for hospitalizations
timeFrame: From randomization until end of treatment (maximum up to 57 months).
measure: Exploratory endpoints: Febrile infections
timeFrame: From randomization until end of treatment (maximum up to 57 months).
measure: Exploratory endpoints: Employment status
timeFrame: From randomization until end of treatment (maximum up to 56 months).
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: iOMEDICO AG
state: Baden-Wuerttemberg
Study officials:
affiliation: Essen University Hospital
name: Anja Welt, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.