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 Elderly Patient (CALHYS)

NCT05664893 | Withdrawn Phase 1 DMC

• 1 other identifier: 2017/78
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Women aged 70 years or older, newly diagnosed for locally advanced unilateral breast cancer, with a histological diagnosis of invasive mammary carcinoma, positive hormone receptors, HER2 status Negative, not immediately operable (stage of disease, comorbidities or refusal of surgery) with tumor in place, with indication of treatment with hormone therapy and hypofractionated radiotherapy, not eligible for neoadjuvant chemotherapy and without major comorbidity contraindicating the proposed treatment regimen.

Conditions

HER2 Negative Breast Cancer Not Immediately Operated

Outcome Measures

Primary Outcomes (2)

• Phase I : determination of Maximal Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) of Ribociclib

  Phase I : the frequencies of adverse events according to the CTCAE 4.03 requiring a dose discontinuation (DLT) 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.

  Phase I : during the 8 weeks of radiotherapy concomitant with the Ribociclib and hormone therapy and during the 3 months of post-radiotherapy follow-up.

• Phase II : evaluation of the efficacy of Ribociclib in association with hormone therapy and hypofractionated radiotherapy

  Phase II :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.

  Phase II : at 24-months

Secondary Outcomes (16)

• overall survival

  24 months

• overall survival

  60 months

• progression free survival

  24 months

• progression free survival

  60 months

• quality of Life (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30)

  60 months

Study Arms (1)

Principal arm

EXPERIMENTAL

registration phase : 3 cycles of 600mg per day of ribociclib Treatment phase : 3 cycles of dose de-escalation of ribociclib (600 or 400 or 200mg per day) Maintenance phase : 600mg per day of ribociclib until 24months of total treatment

Drug: Ribociclib Oral Tablet

Interventions

Ribociclib Oral Tablet DRUG

600mg per day during registration phase (3 cycles); de-escalation phase (600 to 200mg per day associated to radiotherapy) during 3 other cycles; maintenance phase until 24 months of treatment in total (600mg per day). All over th etimme, hormonotherapy is received in concomitance

Principal arm

Eligibility Criteria

• Age: 70 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures;
• Women ≥ 70 years old at the time of signing informed consent;
• Have a performance status of 0 to 2 on the ECOG Performance Scale ;
• Newly diagnosed for non-metastatic unilateral breast cancer;
• Histological diagnosis of invasive mammary carcinoma, positive hormone receptors, HER2 status Negative defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample;
• Not immediately operable (stage of disease, comorbidities or wish to avoid surgery) with tumor in place;
• Measurable disease based on RECIST 1.1 (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation).
• Demonstrate adequate organ functions:
• Hemoglobin \> 9 g/dL;
• Absolute neutrophil count \> 1.5 G/L;
• Platelets \> 100 G/L;
• INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug);
• Total serum bilirubin \< ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome
• AST and ALT \< 2.5 x ULN;
• Alkaline Phosphatase \< 2.5 x ULN

You may not qualify if:

• Patient eligible to resection surgery and wish to proceed with the surgery;
• Patient eligible to neoadjuvant chemotherapy;
• Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition);
• Concomitant bilateral breast cancer;
• Tumor in previously irradiated territory;
• Patient has received any CDK4/6 inhibitor;
• Patient with a known hypersensitivity to any of the excipients of Ribociclib and/or hormono therapy (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy);
• Known additional malignancy. Exceptions include basal cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy;
• Contraindication for hormone therapy , Ribociclib or radiotherapy;
• Severe dementia;
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
• 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.)
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
• History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
• Documented cardiomyopathy

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead

Study Sites (1)

Centre Antoine Lacassagne

Nice, 06189, France

Location

MeSH Terms

Interventions

ribociclib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: step 1 : 600mg of ribociclib step 2 : 400mg of ribociclib step 3 : 200mg of ribociclib

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: December 27, 2022
• Study Start: June 26, 2023
• Primary Completion: March 26, 2026
• Study Completion: March 26, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)