Detect V / CHEVENDO (Chemo vs. Endo)

• ClinicalTrials.gov Identifier: NCT02344472
• Recruitment Status: Recruiting
• First Posted: January 26, 2015
• Last Update Posted: October 25, 2019
• Sponsor: Prof. W. Janni
• Collaborators: Roche Pharma AG; Novartis Pharmaceuticals; Eisai GmbH; Celgene Corporation
• Information provided by (Responsible Party): Prof. W. Janni, University of Ulm

Tracking Information

• First Submitted Date: January 11, 2015
• First Posted Date: January 26, 2015
• Last Update Posted Date: October 25, 2019
• Study Start Date: September 2015
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2019)

Number of Participants with Adverse Events [ Time Frame: 3 - 9 weeks ]

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)

Original Primary Outcome Measures (submitted: January 16, 2015)

Number of Participants with Adverse Events [ Time Frame: 3 - 9 weeks ]

safety of a dual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus endocrine therapy as compared to a dual HER2-targeted therapy with Herceptin® (trastuzumab) and Perjeta® (pertuzumab) plus chemotherapy by the proportion of patients experiencing any adverse event (as defined by the modified adverse event score)

Current Secondary Outcome Measures (submitted: January 16, 2015)

• quality-adjusted survival [ Time Frame: 3 - 9 weeks ]
  to assess quality-adjusted survival (as assessed by the Q-TWiST method) and to compare it between the two treatment arms
• overall response rate (ORR) [ Time Frame: 3 - 9 weeks ]
  compare efficacy between the two treatment arms as assessed by overall response rate (ORR)
• incidence of central nervous system (CNS) metastases and their control rate [ Time Frame: 3 - 9 weeks ]
  assess the incidence of CNS metastases and control rate of preexisting CNS metastases
• Analysis of Quality of life [ Time Frame: 3 - 9 weeks ]
  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
• presence and number of circulating tumor cell (CTC) at different time points [ Time Frame: 6 weeks ]
  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
• Evaluation of all reported events and all grades in both treatment arms (chemotherapy and endocrine therapy) [ Time Frame: 3 - 9 weeks ]
  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
• disease control rate (DCR) [ Time Frame: 3 - 9 weeks ]
  compare efficacy between the two treatment arms as assessed by disease control rate (DCR)
• progression-free survival (PFS) [ Time Frame: 3 - 9 weeks ]
  compare efficacy between the two treatment arms as assessed by progression-free survival (PFS)
• overall survival (OS) [ Time Frame: 3 - 9 weeks ]
  compare efficacy between the two treatment arms as assessed by overall survival (OS)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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.
• Brief Summary: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• Drug: pertuzumab
  HER2 targeted Therapy
  Other Name: Perjeta®
• Drug: Trastuzumab
  HER2 targeted Therapy
  Other Name: Herceptin®
• Drug: Capecitabine
  Chemotherapy
• Drug: Paclitaxel
  Chemotherapy
• Drug: Vinorelbine
  Chemotherapy
• Drug: Docetaxel
  Chemotherapy
• Drug: Exemestane
  endocrine therapy
• Drug: Letrozole
  endocrine therapy
• Drug: Anastrozole
  endocrine therapy
• Drug: Fulvestrant
  endocrine therapy
• Drug: Ribociclib
  CDK 4/6 inhibitor
  Other Name: Kisqali®
• Drug: nab-Paclitaxel
  chemotherapy
• Drug: eribulin
  chemotherapy
• Drug: leuprorelin
  endocrine therapy
• Drug: goserelin
  endocrine therapy

Study Arms

• Experimental: Chemotherapy with docetaxel
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Docetaxel
• Experimental: Chemotherapy with paclitaxel
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Paclitaxel
• Experimental: Chemotherapy with vinorelbine
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Vinorelbine
• Experimental: Chemotherapy with capecitabine
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Capecitabine
• Experimental: endocrine therapy with exemestane
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus exemestane.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Exemestane
  • Drug: Ribociclib
• Experimental: endocrine therapy with fulvestrant
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus fulvestrant.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Fulvestrant
  • Drug: Ribociclib
• Experimental: endocrine therapy with anastrozole
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus anastrozole.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Anastrozole
  • Drug: Ribociclib
• Experimental: endocrine therapy with letrozole
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus letrozole.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Letrozole
  • Drug: Ribociclib
• Experimental: Chemotherapy with nab-Paclitaxel
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: nab-Paclitaxel
• Experimental: Chemotherapy with eribulin
  dual 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).
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: eribulin
• Experimental: endocrine therapy with leuprorelin
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus leuprorelin.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Ribociclib
  • Drug: leuprorelin
• Experimental: endocrine therapy with goserelin
  dual HER2-targeted therapy with Herceptin® (trastuzumab), Perjeta® (pertuzumab) and Kisqali® (Ribociclib) plus goserelin.
  Interventions:

  • Drug: pertuzumab
  • Drug: Trastuzumab
  • Drug: Ribociclib
  • Drug: goserelin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 16, 2015): 270
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wolfgang Janni, MD PhD; +49 731 500 58 501; studienzentrale.ufk@uniklinik-ulm.de

Contact: Sabrina Krause, M. sc.; +49 731 500 58 652; sabrina.krause@uniklinik-ulm.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02344472
• Other Study ID Numbers: D-V; 2014-002249-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Prof. W. Janni, University of Ulm
• Study Sponsor: Prof. W. Janni

Collaborators

• Roche Pharma AG
• Novartis Pharmaceuticals
• Eisai GmbH
• Celgene Corporation

Investigators

• Principal Investigator: Jens Huober, MD PhD; Studienzentrale Dpt. Gyn/OB University Ulm

• PRS Account: University of Ulm
• Verification Date: October 2019