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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06207734
• Other study ID #: DISCUSS
• Status: Recruiting
• Phase: Phase 2
• Start date: January 17, 2024
• Est. completion date: July 10, 2028

Study information

• Verified date: April 2024
• Source: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Contact: Thomas Decker, Prof.
• Phone: +49 751 366197
• Email: Thomas.Decker[@]onkonet.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 10, 2028
• Est. primary completion date: January 10, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 = 1.5 x 109/L

3. Platelets = 100 x 109/L

4. Calculated creatinine clearance = 50 mL/min as determined by the Cockcroft-Gault equation

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

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.

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Germany	Charité Berlin	Berlin
Germany	Onkologische GP Gütersloh	Gütersloh
Germany	Hämatologisch-Onkologische Praxis Altona	Hamburg
Germany	Studienzentrum Onkologie Ravensburg Gmbh	Ravensburg
Germany	Krankenhaus Barmherzige Brüder Regensburg	Regensburg
Germany	Onkologisch-Gastroenterologische Schwerpunktpraxis Innere Medizin GbR	Singen
Germany	Onkologiezentrum Soest-Iserlohn	Soest

Sponsors (1)

Lead Sponsor	Collaborator
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free survival (PFS)	Time from randomization until progress	54 months
Secondary	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
Secondary	Progression-free survival (PFS2)	Time from re-treatment with CDK4/6 inhibitors to clinical disease progression or death from any cause	54 months
Secondary	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
Secondary	Time to first use of chemotherapy	Time to first use of chemotherapy after progression on combined endocrine/CDK4/6 inhibitor treatment	54 months
Secondary	Quality of life (QoL) EORTC QLQ-C30	QoLassessed with the QoL questionnaire EORTC QLQ-C30	54 months
Secondary	Quality of life (QoL) EORTC QLQ-BR23	QoLassessed with the QoL questionnaire EORTC QLQ-BR23	54 months
Secondary	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