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

NCT03811418

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: iOM-110383
  • SECONDARY ID: 2017-004749-25
  • NCT ID: NCT03811418

Conditions

  • Advanced Breast Cancer
  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
TrastuzumabKanjinti®, ABP 980Kanjinti/Pertuzumab plus Vinorelbine
PertuzumabPerjeta®Kanjinti/Pertuzumab plus Vinorelbine
VinorelbineKanjinti/Pertuzumab plus Vinorelbine
DocetaxelKanjinti/Pertuzumab plus Docetaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Kanjinti/Pertuzumab plus VinorelbineExperimentalPatients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine.
  • Trastuzumab
  • Pertuzumab
  • Vinorelbine
Kanjinti/Pertuzumab plus DocetaxelActive ComparatorPatients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel.
  • Trastuzumab
  • Pertuzumab
  • Docetaxel

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Patient-reported health-related quality of life (QoL): FACT-B
Time Frame:Baseline to week 18
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression-free survival (PFS) assessed by the investigator
Time Frame:Baseline, every 12 weeks after randomization (maximum up to 76 months)
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Time from randomization to date of death (maximum up to approximately 76 months)
Safety Issue:
Description: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.
Measure:Overall response rate (ORR)
Time Frame:Baseline, every 12 weeks after randomization (maximum up to 76 months)
Safety Issue:
Description:Overall response rate is defined as the proportion of patients achieving a complete or partial remission as best response.
Measure:Clinical benefit rate (CBR)
Time Frame:Baseline, every 12 weeks after randomization (maximum up to 76 months)
Safety Issue:
Description:CBR is defined as proportion of patients achieving a complete or partial remission or a stable disease lasting at least 24 weeks.
Measure:Time to treatment failure (TTF)
Time Frame:Baseline, every 12 weeks after randomization (maximum up to 56 months)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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).
Measure:Blood count: Hemoglobin
Time Frame:From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:The number of platelets in the blood will be counted as per clinical routine and will be displayed using by-patient listings.
Measure:Blood count: Leukocytes
Time Frame:From date of informed consent to +30 days from last application of study medication (maximum up to 57 months)
Safety Issue:
Description:The number of leukocytes in the blood will be counted as per clinical routine and will be displayed using by-patient listings.
Measure: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 Issue:
Description:The absolute neutrophil count will be determined as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:Coagulation (INR) as per clinical routine will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:Alkaline phosphatase will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:ALT will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:AST will be measured in U/L as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:Total bilirubin will be measured in mg/dL as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:Serum creatinine will be measured in µmol/L as per clinical routine and will be displayed using by-patient listings.
Measure: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)
Safety Issue:
Description:Incidence of clinically relevant LVEF levels. Change from baseline at each assessment time point, worst-on-treatment will be displayed using descriptive statistics.
Measure: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).
Safety Issue:
Description: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.
Measure: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).
Safety Issue:
Description: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.
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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
Measure: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).
Safety Issue:
Description: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.
Measure: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).
Safety Issue:
Description: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
Measure:Exploratory endpoint: Treatment costs
Time Frame:From randomization until end of treatment (maximum up to 56 months).
Safety Issue:
Description:Treatment costs (drug costs)
Measure:Exploratory endpoints: Duration of hospitalizations
Time Frame:From randomization until end of treatment (maximum up to 57 months).
Safety Issue:
Description:Total duration of hospitalizations (per patients)
Measure:Exploratory endpoints: Number of hospitalizations
Time Frame:From randomization until end of treatment (maximum up to 57 months).
Safety Issue:
Description:Number of hospitalizations (in-patient stays)
Measure:Exploratory endpoints: Reasons for hospitalizations
Time Frame:From randomization until end of treatment (maximum up to 57 months).
Safety Issue:
Description:Reasons for hospitalizations
Measure:Exploratory endpoints: Febrile infections
Time Frame:From randomization until end of treatment (maximum up to 57 months).
Safety Issue:
Description:Incidence of febrile infections
Measure:Exploratory endpoints: Employment status
Time Frame:From randomization until end of treatment (maximum up to 56 months).
Safety Issue:
Description:Employment status (kind and duration of sick leaves)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:iOMEDICO AG

Trial Keywords

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

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