Stopping CDK4/6 inhibitors for patients with advanced breast cancer

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

This study is testing whether stopping CDK4/6 inhibitors helps people with advanced breast cancer who have been stable on treatment for a while, while they continue other hormone therapies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 13 sites (Berlin and 12 other locations)
• Trial ID: NCT06207734 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effects of discontinuing CDK4/6 inhibitors in patients with metastatic HR positive, HER2 negative breast cancer who have maintained stable disease after at least 12 months of treatment. The study is designed as a low-intervention, randomized, non-comparative, open-label trial across multiple centers. Participants will either continue their treatment with CDK4/6 inhibitors or discontinue them while continuing endocrine therapy to evaluate long-term disease stabilization.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 18 and older with metastatic HR positive, HER2 negative breast cancer who have shown stable disease after at least 12 months of treatment with CDK4/6 inhibitors.

Not a fit: Patients who have not achieved stable disease after prior treatment or those with curative options available may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the safety and efficacy of stopping CDK4/6 inhibitors, potentially leading to improved treatment strategies for patients with advanced breast cancer.

How similar studies have performed: While there have been studies on CDK4/6 inhibitors, this specific approach of discontinuation after prolonged treatment is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Female patient has given written informed consent
2. Patient is ≥ 18 years of age at time of signing the written informed consent
3. Patient has been diagnosed with histologically confirmed metastatic adenocarcinoma of the breast
4. Patient has documented histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative (HER2-) disease
5. Patient has no curative treatment option by surgery or radiotherapy
6. 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
7. Patient has a preserved performance status (ECOG ≤ 2)
8. Patient has adequate bone marrow, renal and hepatic function:

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

   1. 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
   2. 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
   3. Artificially induced postmenopausal women (by Gonadotropin-releasing hormone \[GnRH\] analogs)
10. WOCBP must have a negative serum pregnancy test within 7 days prior to start of trial

Exclusion Criteria:

1. Patient has active (or history of) brain or leptomeningeal metastases
2. 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.
3. 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
4. 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
5. Patient has contraindication or shows hypersensitivity to the existing treatment with CDK4/6 inhibitor plus endocrine therapy
6. 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
7. 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.
8. 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.
9. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.
10. 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.

Where this trial is running

Berlin and 12 other locations

• Charité Berlin — Berlin, Germany (Recruiting)
• Hämatologische Onkologische Praxis im Medicum — Bremen, Germany (Recruiting)
• St. Johannes Hospital Dortmund — Dortmund, Germany (Active_not_recruiting)
• Praxis und Tagesklinik — Friedrichshafen, Germany (Active_not_recruiting)
• Hausärztliche und Onkologische Gemeinschaftspraxis — Gerlingen, Germany (Recruiting)
• Onkologische GP Gütersloh — Gütersloh, Germany (Active_not_recruiting)
• Hämatologisch-Onkologische Praxis Altona — Hamburg, Germany (Recruiting)
• Universitätsmedizin der Johannes Gutenberg-Universität Mainz — Mainz, Germany (Recruiting)
• MVZ für Hämatologie und Onkologie der MVZ Mülheim GmbH — Mülheim, Germany (Recruiting)
• MVZ für Hämatologie und Onkologie — Ravensburg, Germany (Recruiting)
• Krankenhaus Barmherzige Brüder Regensburg — Regensburg, Germany (Recruiting)
• Onkologisch-Gastroenterologische Schwerpunktpraxis Innere Medizin GbR — Singen, Germany (Recruiting)
• Onkologiezentrum Soest-Iserlohn — Soest, Germany (Recruiting)

Study contacts

• Study coordinator: Thomas Decker, Prof.

Conditions Breast Cancer; Metastatic HR positive, HER2 negative breast cancer; CDK4/6 inhibitors; Endocrine therapy