Detect V / CHEVENDO (Chemo vs. Endo)

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof. W. Janni
• Collaborators: Celgene Corporation; DETECT study group; Eisai GmbH; Novartis Pharmaceuticals; Roche Pharma AG
• Treatments: Albumin-Bound Paclitaxel; Anastrozole; Capecitabine; Docetaxel; Estradiol; Exemestane; Fulvestrant; Goserelin; Letrozole; Leuprolide; Paclitaxel; Pertuzumab; Tamoxifen; Trastuzumab; Vinorelbine

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