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

NCT06207734 | Recruiting Phase 2

• 1 other identifier: DISCUSS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Progression-free survival (PFS)

  54 months

• Time to treatment failure (TTF)

  54 months

• Progression-free survival (PFS2)

  54 months

• Time to treatment failure (TTF2)

  54 months

• Time to first use of chemotherapy

  54 months

Study Arms (2)

Control arm CDK4/6 continuation

ACTIVE COMPARATOR

* Continuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment

Drug: Continuation of CDK4/6 inhibitor Palbociclib; Drug: Continuation of CDK4/6 inhibitor -Palbociclib; Drug: Continuation of CDK4/6 inhibitor Abemaciclib

Experimental arm CDK4/6 inhibitor discontinuation

EXPERIMENTAL

* Discontinuation of CDK4/6 inhibitor treatment * Continuation of endocrine treatment

Drug: Discontinuation of CDK4/6 inhibitor Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor -Palbociclib; Drug: Discontinuation of CDK4/6 inhibitor Abemaciclib

Interventions

Continuation of CDK4/6 inhibitor -Palbociclib DRUG

Continuation of CDK4/6 inhibitor -Palbociclib

Also known as: Study treatment

Control arm CDK4/6 continuation

Discontinuation of CDK4/6 inhibitor -Palbociclib DRUG

Discontinuation of CDK4/6 inhibitor -Palbociclib

Also known as: Study treatment

Experimental arm CDK4/6 inhibitor discontinuation

Continuation of CDK4/6 inhibitor Abemaciclib DRUG

Continuation of CDK4/6 inhibitor Abemaciclib

Also known as: Study treatment

Control arm CDK4/6 continuation

Discontinuation of CDK4/6 inhibitor Abemaciclib DRUG

Discontinuation of CDK4/6 inhibitor Abemaciclib

Also known as: Study treatment

Experimental arm CDK4/6 inhibitor discontinuation

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (13)

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, 88212, Germany

RECRUITING

Krankenhaus Barmherzige Brüder Regensburg

Regensburg, Germany

RECRUITING

Onkologisch-Gastroenterologische Schwerpunktpraxis Innere Medizin GbR

Singen, 78224, Germany

RECRUITING

Onkologiezentrum Soest-Iserlohn

Soest, 59494, Germany

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Salah-Eddin Al-Batran, Prof.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Central Study Contacts

Thomas Decker, Prof.

CONTACT

+49 751 366197; Thomas.Decker@onkonet.eu

Regina Eickhoff, Dr.

CONTACT

+49 69 / 5899 787; eickhoff.regina@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 17, 2024
• Study Start: January 17, 2024
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): July 10, 2028
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (13)