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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut fuer Klinische Krebsforschung IKF GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jan 2024 → ongoing

Decision date (initial)

2023-11-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

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.

Conditions and MedDRA coding

Metastatic HR positive, HER2 negative breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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

Exclusion criteria 10

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 IMP 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 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
6. 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
7. 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
8. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities
9. 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
10. Patient has contraindication or shows hypersensitivity to the existing treatment with CDK4/6 inhibitor plus endocrine therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival rate 12 months after randomization (PFS@12_stopping), defined as proportion of patients alive and without progression according to radiologic imaging assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut fuer Klinische Krebsforschung IKF GmbH

Sponsor organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Address

Steinbacher Hohl 2-26, Praunheim Praunheim

City

Frankfurt Am Main

Postcode

60488

Country

Germany

Scientific contact point

Organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical trial project manager

Public contact point

Organisation

Institut fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical trial project manager

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications