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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Continuation of CDK4/6 inhibitor Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor Palbociclib; Drug: Continuation of CDK4/6 inhibitor -Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor -Palbociclib; Drug: Continuation of CDK4/6 inhibitor Abemaciclib; Drug: Discontinuation of CDK4/6 inhibitor Abemaciclib

• Registration Number: NCT06207734
• Lead Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Brief Summary

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.

Study Timeline

• Study First Submitted: 2024-01-03
• Study First Submitted QC: 2024-01-12
• Study Start: 2024-01-17
• Study First Posted: 2024-01-17
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-01
• Primary Completion: 2027-01-10
• Study Completion: 2028-07-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm CDK4/6 continuation	Continuation of CDK4/6 inhibitor Palbociclib	* Continuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment
Control arm CDK4/6 continuation	Continuation of CDK4/6 inhibitor -Palbociclib	* Continuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment
Control arm CDK4/6 continuation	Continuation of CDK4/6 inhibitor Abemaciclib	* Continuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment
Experimental arm CDK4/6 inhibitor discontinuation	Discontinuation of CDK4/6 inhibitor Palbociclib	* Discontinuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment
Experimental arm CDK4/6 inhibitor discontinuation	Discontinuation of CDK4/6 inhibitor -Palbociclib	* Discontinuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment
Experimental arm CDK4/6 inhibitor discontinuation	Discontinuation of CDK4/6 inhibitor Abemaciclib	* Discontinuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment

Primary Outcome Measures

Name	Time	Method
Progression-free survival rate 12 months after randomization (PFS@12_stopping)	12 months	Proportion of patients alive and without progression according to radiologic imaging assessment

Secondary Outcome Measures

Name	Time	Method
Quality of life (QoL) EORTC QLQ-BR23	54 months	QoLassessed with the QoL questionnaire EORTC QLQ-BR23
Time to treatment failure (TTF2)	54 months	Time to end of treatment because of patient's wish, investigator's decision, toxicity, or clinical progression after re-treatment with CDK4/6 inhibitors
Time to first use of chemotherapy	54 months	Time to first use of chemotherapy after progression on combined endocrine/CDK4/6 inhibitor treatment
Quality of life (QoL) EORTC QLQ-C30	54 months	QoLassessed with the QoL questionnaire EORTC QLQ-C30
Progression-free survival (PFS)	54 months	Time from randomization until progress
Time to treatment failure (TTF)	54 months	Time from randomization to end of treatment because of patient's wish, investigator's decision, toxicity, or progression
Progression-free survival (PFS2)	54 months	Time from re-treatment with CDK4/6 inhibitors to clinical disease progression or death from any cause
Safety (rate of adverse events)	54 months	Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs) graded according to NCI CTCAE v5.0

Trial Locations

Locations (13)

MVZ für Hämatologie und Onkologie der MVZ Mülheim GmbH; 🇩🇪 Mülheim, Germany

Onkologische GP Gütersloh; 🇩🇪 Gütersloh, Germany

Hämatologisch-Onkologische Praxis Altona; 🇩🇪 Hamburg, Germany

Krankenhaus Barmherzige Brüder Regensburg; 🇩🇪 Regensburg, Germany

Hämatologische Onkologische Praxis im Medicum; 🇩🇪 Bremen, Germany

St. Johannes Hospital Dortmund; 🇩🇪 Dortmund, Germany

Praxis und Tagesklinik; 🇩🇪 Friedrichshafen, Germany

Hausärztliche und Onkologische Gemeinschaftspraxis; 🇩🇪 Gerlingen, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz; 🇩🇪 Mainz, Germany

Charité Berlin; 🇩🇪 Berlin, Germany

MVZ für Hämatologie und Onkologie; 🇩🇪 Ravensburg, Germany

Onkologisch-Gastroenterologische Schwerpunktpraxis Innere Medizin GbR; 🇩🇪 Singen, Germany

Onkologiezentrum Soest-Iserlohn; 🇩🇪 Soest, Germany