Discontinuation of CDK4/6 Inhibitors in Patients With Metastatic HR Positive, HER2 Negative Breast Cancer

Official title

Discontinuation of CDK4/6 Inhibitors in Patients With Metastatic HR Positive, HER2 Negative Breast Cancer With Durable Disease Control: A Randomized Low-intervention Phase II Trial of the AIO Working Groups Breast Cancer and Quality of Life

Overview

This is a low-intervention, randomized, non-comparative, open-label, multicenter, prospective, phase II trial investigating discontinuation of CDK4/6 inhibitors in patients with metastatic HR positive, HER2 negative breast cancer with durable disease control.

Detailed description

The primary objective is to evaluate long-term disease stabilization of CDK4/6 inhibitors discontinuation after a prolonged treatment period with continued endocrine therapy in breast cancer patients exhibiting at least stable disease after at least 12 months of combination treatment.

Interventions

• Drug Continuation of CDK4/6 inhibitor Palbociclib
  Continuation of CDK4/6 inhibitor Palbociclib
• Drug Discontinuation of CDK4/6 inhibitor Palbociclib
  Discontinuation of CDK4/6 inhibitor Palbociclib
• Drug Continuation of CDK4/6 inhibitor -Palbociclib
  Continuation of CDK4/6 inhibitor -Palbociclib
• Drug Discontinuation of CDK4/6 inhibitor -Palbociclib
  Discontinuation of CDK4/6 inhibitor -Palbociclib
• Drug Continuation of CDK4/6 inhibitor Abemaciclib
  Continuation of CDK4/6 inhibitor Abemaciclib
• Drug Discontinuation of CDK4/6 inhibitor Abemaciclib
  Discontinuation of CDK4/6 inhibitor Abemaciclib

Primary outcome measures

• Progression-free survival rate 12 months after randomization (PFS@12_stopping) [Time frame: 12 months]

Secondary outcome measures (8)

• Progression-free survival (PFS) [Time frame: 54 months]
• Time to treatment failure (TTF) [Time frame: 54 months]
• Progression-free survival (PFS2) [Time frame: 54 months]
• Time to treatment failure (TTF2) [Time frame: 54 months]
• Time to first use of chemotherapy [Time frame: 54 months]
• Quality of life (QoL) EORTC QLQ-C30 [Time frame: 54 months]
• Quality of life (QoL) EORTC QLQ-BR23 [Time frame: 54 months]
• Safety (rate of adverse events) [Time frame: 54 months]

Eligibility criteria

Inclusion criteria

• Female patient has given written informed consent
• Patient is ≥ 18 years of age at time of signing the written informed consent
• Patient has been diagnosed with histologically confirmed metastatic adenocarcinoma of the breast
• Patient has documented histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative (HER2-) disease
• Patient has no curative treatment option by surgery or radiotherapy
• Patient was treated with CDK4/6 inhibitor plus endocrine therapy for at least 12 months with disease control (complete remission, partial remission or stable disease) as judged by the treating physician before planned study treatment initiation
• Patient has a preserved performance status (ECOG ≤ 2)
• Patient has adequate bone marrow, renal and hepatic function:

• Hemoglobin > 9.0 g/dL
• Absolute neutrophil count judged as appropriate for study therapy by the investigator
• Platelets ≥ 100 x 109/L
• Calculated creatinine clearance judged as appropriate for study therapy by the investigator
• AST (SGOT) / ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN
• Serum albumin > 30 g/L
• Patients considered postmenopausal according to one of the following definition:

• Women <50 years of age who are amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and whose levels of luteinizing hormone and follicle-stimulating hormone are in the post-menopausal institutional range
• Women ≥50 years of age who are amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago or had chemotherapy-induced menopause with last menses >1 year ago
• Artificially induced postmenopausal women (by Gonadotropin-releasing hormone \[GnRH\] analogs)
• WOCBP must have a negative serum pregnancy test within 7 days prior to start of trial

Exclusion criteria

• Patient has active (or history of) brain or leptomeningeal metastases
• Patient is pre- or perimenopausal. Patient is pregnant or breast feeding or planning to become pregnant within five times the half-life of the IMPs after the end of treatment.
• Patient has significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction or cerebrovascular accident within 6 months prior to initiation of study treatment, unstable arrhythmias, or unstable angina
• Patient has other concomitant or previous malignancy, except adequately treated in-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, cancer in complete remission for > 5 years
• Patient has contraindication or shows hypersensitivity to the existing treatment with CDK4/6 inhibitor plus endocrine therapy
• Patient shows evidence of any other disease, neurologic or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of any of the study medications, puts the patient at higher risk for treatment-related complications or may affect the interpretation of study results
• Patient participated in another clinical study with an investigational medicinal product during the last 28 days before treatment initiation or 7 half-lives of previously used trial medication, whichever is longer or participate in such a study at the same time as this trial.

Note: Participation in non-interventional clinical studies or registries is allowed.

• Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.
• Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.
• Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 13 centers

• Charité Berlin — Berlin
• Hämatologische Onkologische Praxis im Medicum — Bremen
• St. Johannes Hospital Dortmund — Dortmund
• Praxis und Tagesklinik — Friedrichshafen
• Hausärztliche und Onkologische Gemeinschaftspraxis — Gerlingen
• Onkologische GP Gütersloh — Gütersloh
• Hämatologisch-Onkologische Praxis Altona — Hamburg
• Universitätsmedizin der Johannes Gutenberg-Universität Mainz — Mainz
• … and 5 more centers

Identifiers

NCT: NCT06207734 · DISCUSS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗