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

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Continuation of CDK4/6 inhibitor Palbociclib; Drug: Continuation of CDK4/6 inhibitor -Palbociclib; Drug: Continuation of CDK4/6 inhibitor Abemaciclib; Drug: Discontinuation of CDK4/6 inhibitor Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor -Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor Abemaciclib

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Thomas Decker, Prof.; Phone Number: +49 751 366197; Email: Thomas.Decker@onkonet.eu
• Study Contact Backup: Name: Regina Eickhoff, Dr.; Phone Number: 33 +49 69 / 5899 787; Email: eickhoff.regina@ikf-khnw.de

Study Locations

• Germany
  • Berlin, Germany
    • Recruiting
    • Charite Berlin
  • Bremen, Germany
    • Recruiting
    • Hamatologische Onkologische Praxis Im Medicum
  • Dortmund, Germany
    • Active, not recruiting
    • St. Johannes Hospital Dortmund
  • Friedrichshafen, Germany
    • Active, not recruiting
    • Praxis und Tagesklinik
  • Gerlingen, Germany
    • Recruiting
    • Hausärztliche und Onkologische Gemeinschaftspraxis
  • Gütersloh, Germany
    • Active, not recruiting
    • Onkologische GP Gütersloh
  • Hamburg, Germany
    • Recruiting
    • Hämatologisch-Onkologische Praxis Altona
  • Mainz, Germany
    • Recruiting
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Mülheim, Germany
    • Recruiting
    • MVZ für Hämatologie und Onkologie der MVZ Mülheim GmbH
  • Ravensburg, Germany, 88212
    • Recruiting
    • MVZ für Hämatologie und Onkologie
    • Contact: Thomas Decker, Prof.
  • Regensburg, Germany
    • Recruiting
    • Krankenhaus Barmherzige Brüder Regensburg
  • Singen, Germany, 78224
    • Recruiting
    • Onkologisch-Gastroenterologische Schwerpunktpraxis Innere Medizin GbR
  • Soest, Germany, 59494
    • Recruiting
    • Onkologiezentrum Soest-Iserlohn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm CDK4/6 continuation; Continuation of CDK4/6 inhibitor treatment; Continuation of endocrine treatment	Drug: Continuation of CDK4/6 inhibitor Palbociclib; Continuation of CDK4/6 inhibitor Palbociclib; Other Names: Study treatment; Drug: Continuation of CDK4/6 inhibitor -Palbociclib; Continuation of CDK4/6 inhibitor -Palbociclib; Other Names: Study treatment; Drug: Continuation of CDK4/6 inhibitor Abemaciclib; Continuation of CDK4/6 inhibitor Abemaciclib; Other Names: Study treatment
Experimental: Experimental arm CDK4/6 inhibitor discontinuation; Discontinuation of CDK4/6 inhibitor treatment; Continuation of endocrine treatment	Drug: Discontinuation of CDK4/6 inhibitor Palbociclib; Discontinuation of CDK4/6 inhibitor Palbociclib; Other Names: Study treatment; Drug: Discontinuation of CDK4/6 inhibitor -Palbociclib; Discontinuation of CDK4/6 inhibitor -Palbociclib; Other Names: Study treatment; Drug: Discontinuation of CDK4/6 inhibitor Abemaciclib; Discontinuation of CDK4/6 inhibitor Abemaciclib; Other Names: Study treatment

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Investigators: Study Director: Salah-Eddin Al-Batran, Prof., Frankfurter Institut für Klinische Krebsforschung IKF GmbH

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): July 10, 2028

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Endocrine therapy; CDK4/6 inhibitors; Metastatic HR positive, HER2 negative breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: DISCUSS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No