Clinical Trials /

Detect V / CHEVENDO (Chemo vs. Endo)

NCT02344472

Description:

Chemo- versus endocrine therapy in combination with dual HER2-targeted therapy of Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus Kisqali® (ribociclib) in patients with HER2 positive and hormone-receptor positive metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Detect V / CHEVENDO (Chemo vs. Endo)
  • Official Title: DETECT V / CHEVENDO A Multicenter, Randomized Phase III Study to Compare Chemo- Versus Endocrine Therapy in Combination With Dual HER2-targeted Therapy of Herceptin® (Trastuzumab) and Perjeta® (Pertuzumab) Plus Kisqali® (Ribociclib) in Patients With HER2 Positive and Hormone-receptor Positive Metastatic Breast Cancer.

Clinical Trial IDs

  • ORG STUDY ID: D-V
  • SECONDARY ID: 2014-002249-22
  • NCT ID: NCT02344472

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
pertuzumabPerjeta®Chemotherapy with capecitabine
TrastuzumabHerceptin®Chemotherapy with capecitabine
CapecitabineChemotherapy with capecitabine
PaclitaxelChemotherapy with paclitaxel
VinorelbineChemotherapy with vinorelbine
DocetaxelChemotherapy with docetaxel
Exemestaneendocrine therapy with exemestane
Letrozoleendocrine therapy with letrozole
Anastrozoleendocrine therapy with anastrozole
Fulvestrantendocrine therapy with fulvestrant
RibociclibKisqali®endocrine therapy with anastrozole
nab-PaclitaxelChemotherapy with nab-Paclitaxel
eribulinChemotherapy with eribulin
leuprorelinendocrine therapy with leuprorelin
goserelinendocrine therapy with goserelin

Purpose

Chemo- versus endocrine therapy in combination with dual HER2-targeted therapy of Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus Kisqali® (ribociclib) in patients with HER2 positive and hormone-receptor positive metastatic breast cancer.

Detailed Description

      Especially for diseases that are not curable such as metastatic breast cancer (MBC), the
      maintenance of quality of life is one of the main aims of treatments. Adverse events are
      well-known side effects of any cytostatic treatment and impact the patients' quality of life.
      Therefore, new treatment options are developed that should stop or at least slow down
      metastatic spread of cancer without causing negative side effects in terms of high-grade
      adverse events. For patients with hormone-receptor positive and HER2 positive MBC the
      combination of HER2-targeted therapy with endocrine therapy has already been proven to be an
      effective and in many cases valuable alternative to the combination of HER2-targeted therapy
      with chemotherapy. The high relevance of HER2-neu-targeted/endocrine treatment combinations
      derives from the fact that potential chemotherapy-related toxicity can be avoided, which in
      turn positively affects quality of life. Clinical trials suggest an additional benefit when a
      CDK4/6 inhibitor is added to the combination of endocrine therapy and anti HER2 treatment.
      DETECT V is a randomized phase III study comparing the safety and efficacy of trastuzumab
      plus pertuzumab and the CDK 4/6 inhibitor ribociclib in combination with either endocrine
      therapy or chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Chemotherapy with docetaxelExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus docetaxel. Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • Docetaxel
Chemotherapy with paclitaxelExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus paclitaxel.Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • Paclitaxel
Chemotherapy with vinorelbineExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus vinorelbine. Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • Vinorelbine
Chemotherapy with capecitabineExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus capecitabine. Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • Capecitabine
endocrine therapy with exemestaneExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus exemestane.
  • pertuzumab
  • Trastuzumab
  • Exemestane
  • Ribociclib
endocrine therapy with fulvestrantExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus fulvestrant.
  • pertuzumab
  • Trastuzumab
  • Fulvestrant
  • Ribociclib
endocrine therapy with anastrozoleExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus anastrozole.
  • pertuzumab
  • Trastuzumab
  • Anastrozole
  • Ribociclib
endocrine therapy with letrozoleExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus letrozole.
  • pertuzumab
  • Trastuzumab
  • Letrozole
  • Ribociclib
Chemotherapy with nab-PaclitaxelExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus nab-Paclitaxel. Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • nab-Paclitaxel
Chemotherapy with eribulinExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus eribulin. Up to three weeks after completion of chemotherapy, patients will be treated with maintenance endocrine therapy plus dual HER2-targeted therapy and Kisqali® (Ribociclib).
  • pertuzumab
  • Trastuzumab
  • eribulin
endocrine therapy with leuprorelinExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus leuprorelin.
  • pertuzumab
  • Trastuzumab
  • Ribociclib
  • leuprorelin
endocrine therapy with goserelinExperimentaldual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus goserelin.
  • pertuzumab
  • Trastuzumab
  • Ribociclib
  • goserelin

Eligibility Criteria

        Inclusion criteria:

          -  Signed, written informed consent in study participation

          -  The primary tumor and/or biopsies from metastatic sites or locoregional recurrences
             have been confirmed as HER2-positive (FISH-positive or IHC 3+) and hormone receptor
             positive breast cancer by histopathology according to local testing

          -  Metastatic breast cancer or locally advanced BC, which cannot be treated by surgery or
             radiotherapy only

          -  Pre- and postmenopausal women are allowed

          -  No more than two prior chemotherapies for metastatic disease

          -  No more than two prior anti-HER2 therapies for metastatic disease

          -  Pertuzumab retreatment is allowed if prior pertuzumab treatment was finished 12 months
             before

          -  At least one measurable lesion assessable using standard techniques by Response
             Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

          -  Tumor evaluation according to RECIST version 1.1 has been performed within 4 weeks
             before randomization based on local assessment

          -  Age ≥ 18 years

          -  Standard 12-lead ECG values assessed by the local laboratory:

               -  QTcF interval at screening < 450 msec (using Fridericia's correction)

               -  Resting heart rate 50-90 bpm

          -  Left ventricular cardiac ejection fraction (LVEF) ≥ 50% at baseline (as measured by
             echocardiogram)

          -  ECOG Score ≤ 2

          -  Adequate organ function within 14 days before randomization, evidenced by the
             following laboratory results below:

               -  absolute neutrophil count ≥ 1500 cells/µL,

               -  platelet count ≥ 100000 cells/µL,

               -  hemoglobin ≥ 9 g/dL,

               -  ALT (SGPT) ≤ 2.0 × ULN (≤ 3.0 × ULN in case of liver metastases)

               -  AST (SGOT) ≤ 2.0 × ULN (≤ 3.0 × ULN in case of liver metastases)

               -  bilirubin ≤ 1.5 × ULN (with the exception of Gilbert's syndrome)

               -  creatinine ≤ 2.0 mg/dl or 177µmol/L INR ≤ 1,5

          -  Patients must have the following laboratory values within normal limits or corrected
             to within normal limits with supplemets before the first dose of study medication:

               -  Sodium

               -  Potassium

               -  Total calcium

          -  In case of patients of child bearing potential:

        Negative serum pregnancy test at baseline (within 7 days prior to randomization) and
        agreement to remain abstinent (if it is in line with the preferred and usual lifestyle) or
        use single or combined non-hormonal contraceptive methods that result in a failure rate of
        < 1% per year during the treatment period and for at least 7 months after the last dose of
        study treatment

        Exclusion criteria:

        Patients will be excluded from the study for any of the following reasons:

          -  History of hypersensitivity reactions attributed to trastuzumab, pertuzumab,
             ribociclib or to other components of drug formulation

          -  Mandatory need for cytostatic treatment at time of study entry based on clinical
             judgment and national/international treatment guidelines

          -  Known CNS metastases

          -  Any concurrent severe, uncontrolled systemic disease, social or psychiatric condition
             that might interfere with the planned treatment and with the patient's adherence to
             the protocol

          -  Progression on prior Pertuzumab therapy

          -  Treatment with Pertuzumab within the last 12 months

          -  Prior treatment with any mTOR- or CDK4/6-inhibitor

          -  Treatment with any other investigational agents during trial

          -  Known hypersensitivity to lecithin (soya) or peanuts

          -  Life expectancy < 6 months

          -  Patients with pre-existing grade ≥2 peripheral neuropathy are excluded from
             taxane-based chemotherapy

          -  History of serious cardiac disease, including but not confined to:

               -  history of documented heart failure or systolic dysfunction (LVEF < 50%)

               -  high-risk uncontrolled arrhythmias i.e., atrial tachycardia with a heart rate
                  ≥100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
                  higher-grade AV-block (second degree AV-block Type 2 [Mobitz 2] or third degree
                  AV-block)

               -  angina pectoris requiring anti-anginal medication

               -  clinically significant valvular heart disease

               -  evidence of transmural infarction on ECG

               -  poorly controlled hypertension (e.g., systolic >180 mm Hg or diastolic >100 mm
                  Hg)

               -  any other cardiac condition, which in the opinion of the treating physician would
                  make this protocol unreasonably hazardous for the patient

          -  Dyspnea at rest or other diseases that require continuous oxygen therapy

          -  Patients with poorly controlled diabetes or with evidence of clinically significant
             diabetic vascular complications

          -  Patients with known infection with HIV, hepatitis B virus, or hepatitis C virus

          -  Male patients

          -  Pregnant, lactating or women of childbearing potential without a negative pregnancy
             test (serum) within 7 days prior to randomization, irrespective of the method of
             contraception used

          -  Medical or psychological conditions that would not permit the subject to complete the
             study or sign informed consent

          -  Participation in another clinical study within the 30 days before registration

          -  Legal incapacity or limited legal capacity
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events
Time Frame:3 - 9 weeks
Safety Issue:
Description:safety of a dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (riobciclib) plus endocrine therapy as compared to a dual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus chemotherapy (followed by endocrine therapy plus ribociclib in combination with trastuzumab and pertuzumab as maintenance therapy) by the proportion of patients experiencing any adverse event (as defined by the modified adverse event score)

Secondary Outcome Measures

Measure:quality-adjusted survival
Time Frame:3 - 9 weeks
Safety Issue:
Description:to assess quality-adjusted survival (as assessed by the Q-TWiST method) and to compare it between the two treatment arms
Measure:overall response rate (ORR)
Time Frame:3 - 9 weeks
Safety Issue:
Description:compare efficacy between the two treatment arms as assessed by overall response rate (ORR)
Measure:incidence of central nervous system (CNS) metastases and their control rate
Time Frame:3 - 9 weeks
Safety Issue:
Description:assess the incidence of CNS metastases and control rate of preexisting CNS metastases
Measure:Analysis of Quality of life
Time Frame:3 - 9 weeks
Safety Issue:
Description:assess additional aspects of quality of life based on the evaluation of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) QLQ-C30 and QLQ-BR23 questionnaires
Measure:presence and number of circulating tumor cell (CTC) at different time points
Time Frame:6 weeks
Safety Issue:
Description:determine presence and number of CTC in the peripheral blood at baseline and at different time points after the start of palliative treatment including the time of progression, and to assess the value of CTCs as indicator for therapy success
Measure:Evaluation of all reported events and all grades in both treatment arms (chemotherapy and endocrine therapy)
Time Frame:3 - 9 weeks
Safety Issue:
Description:All reported events with all grades for evaluation of safety and tolerability of the study treatments and to to evaluate and compare toxicity of chemotherapy arm vs. endocrine treatment arm
Measure:disease control rate (DCR)
Time Frame:3 - 9 weeks
Safety Issue:
Description:compare efficacy between the two treatment arms as assessed by disease control rate (DCR)
Measure:progression-free survival (PFS)
Time Frame:3 - 9 weeks
Safety Issue:
Description:compare efficacy between the two treatment arms as assessed by progression-free survival (PFS)
Measure:overall survival (OS)
Time Frame:3 - 9 weeks
Safety Issue:
Description:compare efficacy between the two treatment arms as assessed by overall survival (OS)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Prof. W. Janni

Trial Keywords

  • MBC
  • HER2
  • CTC
  • endocrine therapy
  • Pertuzumab
  • Trastuzumab
  • HER2 therapy
  • Ribociclib

Last Updated

October 23, 2019