Phase I/II study to determine the safety and efficacy of Ribociclib in combination with hormone therapy and hypofractionated radiotherapy in breast cancer, with positive hormone receptors and negative HER2 status, in newly diagnosed, not immediately operable (or wishing to avoid surgery), elderly patient

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Antoine Lacassagne

Participant type

Patients

Age range

65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2025 → 26 Mar 2026

Decision date (initial)

2023-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Dose response

• Phase 1:
The main objective for the Phase I is to determine the Maximal Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) of Ribociclib in combination with hormone therapy and hypofractionated radiotherapy in elderly population.
• Phase 2 :
The main objective for the Phase II is to evaluate the efficacy of Ribociclib in association with hormone therapy and hypofractionated radiotherapy in elderly population.

Secondary objectives 6

1. Evaluate overall tolerance of Ribociclib in association with radiotherapy;
2. Evaluate overall survival (OS) at 24 and 60 months;
3. Evaluate progression free survival (PFS) at 24 and 60 months;
4. Evaluate quality of Life;
5. Evaluate compliance to Ribociclib;
6. Evaluate the medical, psychosocial and functional health status of the patients

Conditions and MedDRA coding

breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Patient registered in the study-screening phase;
2. 2. Patient receiving, during the screening phase, 3 cycles of Ribociclib at 600mg without dose decreased;
3. 3. Have a performance status of 0 to 2 on the ECOG Performance Scale;
4. 4. Not immediately operable (stage of disease, comorbidities or refusal of surgery) with tumor in place;
5. 5. Measurable disease based on RECIST 1.1;
6. 6. Demonstrate adequate organ functions: Hemoglobin > 9 g/dL; Absolute neutrophil count > 1.5 G/L; Platelets > 100 G/L; etc...
7. 7. Standard 12-lead ECG values defined as the mean of the triplicate ECGs • QTcF interval at screening < 450 msec (QT interval using Fridericia’s correction) • Mean resting heart rate 50-90 bpm (determined from the ECG)Indication of treatment with hormone therapy and hypofractioned radiotherapy;
8. 8. Patients having taken cognizance of the information sheet and having signed the informed consent;
9. 9. Patients covered by medical insurance.
10. 10. Must be able to swallow ribociclib;
11. 11. Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures
12. 12. Must be willing to remain at the clinical site as required by the protocol.

Exclusion criteria 9

1. 1. Patient eligible to resection surgery after 3 cycles of Ribociclib;
2. 2. Patient eligible to neoadjuvant chemotherapy;
3. 3. Concomitant bilateral breast cancer;
4. 4. Known additional malignancy. Exceptions include basal cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy;
5. 5. Contraindication for hormone therapy, Ribobociblib or radiotherapy;
6. 6. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
7. 7. Severe dementia;
8. 8. Patients unable to express their consent;
9. 9. Vulnerable persons as defined by article L1121-5 - 8: a. Pregnant women, women in labor or breast-feeding mothers, persons deprived of their freedom by judicial or administrative decision, persons hospitalized without their consent by virtue of articles L. 3212-1 and L. 3213-1 and who are not subject to the provisions of article L. 1121-8; b. Persons admitted to a social or health facility for reasons other than research; c. Adults subject to a legal protection order or unable to give their consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. • Phase 1 For this purpose (primary end-point), the frequencies of the toxicity limiting doses will be determined during the 8 weeks of radiotherapy concomitant with the Ribociclib and hormone therapy and during the 3 months of post-radiotherapy follow-up. Toxicities are considered to be limiting if they are leading to discontinuation of treatment (cf dose adaptation in paragraph 6.4.1). The toxicities will be evaluated according to the CTCAE V4.03 scale.
2. • Phase 2:The primary endpoint will be the rate of non-progression at 24-months, defined as the percentage of patients who are alive and have not progressed 24 months after the completion of the Ribociclib and Radiotherapy concomitant phase. The objective response rate will be defined as the sum of complete response and partial response 24 months after the end of the Ribociclib and Radiotherapy concomitant phase divided by the number of evaluable patients.

Secondary endpoints 6

1. The overall tolerance of Ribociclib during the patient’s length of participation will be evaluated using clinical and biological assessment and graded according to the CTCAE V4.03 scale.
2. The overall survival at 24 and 60 months after the end of Ribociclib and Radiotherapy concomitant phase is defined as the time from the inclusion to death whatever the causes. Patients alive or lost at time of analysis will be censored at the date of the last known contact.
3. The progression free survival at 24 and 60 months after the Ribociclib and Radiotherapy concomitant phase is defined as the time from the inclusion to progression, or death due to any cause whatever occurred first.
4. The quality of life will be assessed with QLQ-C30, ELD14, and visual analog scale for pain severity measurement every 6 months until end of follow up.
5. The treatment compliance will be assessed with the 8-item Morisky Medication Adherence Scale
6. The patient’s health status will be evaluated at inclusion with the Onco-geriatric questionnaire G8, clinical score to predict the early death at 100 days, Lee score, ADL, IADL, HS, Charlson, MNA, percentage of weight loss, MMSE, GDSA, Balducci, walking speed and then at 2 and 6 months and progression with the Onco-geriatric questionnaire MMSE, ADL, IADL, walking speed, percentage of weight loss, HS.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Antoine Lacassagne

Sponsor organisation

Centre Antoine Lacassagne

Address

33 Avenue De Valombrose

City

Nice Cedex 2

Postcode

06189

Country

France

Scientific contact point

Organisation

Centre Antoine Lacassagne

Contact name

Director of the Delegation for Clinical Research

Public contact point

Organisation

Centre Antoine Lacassagne

Contact name

Director of the Delegation for Clinical Research

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 44 files

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

Application history

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