HER2 Negative Breast Cancer Not Immediately OperatedPhase 1/2CALHYSNCT05664893
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)
A Phase 1/2 study testing Ribociclib Oral Tablet in people with HER2 Negative Breast Cancer Not Immediately Operated, run by Centre Antoine Lacassagne at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 70 years and older, women only
- Conditions the study is for
- HER2 Negative Breast Cancer Not Immediately Operated
- What is being tested?
- Ribociclib Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 26 Jun 2023to 26 Mar 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- Women only
- No healthy volunteers
- Older adult
Who may be able to join
None listed.
Who cannot join
- 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;
- Previous treatment, in the 2 years before inclusion, by chemotherapy, hormone therapy (more than 6 months before study registration), thoracic surgery or radiotherapy for a malignant tumor;
- Tumor in previously irradiated territory;
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- 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
- Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
- Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug)
- Inability to determine the QTcF interval
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- Systolic Blood Pressure (SBP) \>160 or \<90 mmHg
- Patient is currently receiving any of the following substances within 7 days before randomization:
- Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pomelos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5;
- Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5;
- Vulnerable persons as defined by article L1121-5 - 8:
- 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
- Persons admitted to a social or health facility for reasons other than research;
- Adults subject to a legal protection order or unable to give their consent.
- Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment.
- Criteria for the Ribociclib and Radiotherapy concomitant phase Inclusion criteria
- Patient registered in the study-screening phase;
- Patient receiving, during the registration phase, 3 cycles of Ribociclib at 600mg without dose decreased;
- Have a performance status of 0 to 2 on the ECOG Performance Scale;
- Not immediately operable (stage of disease, comorbidities or refusal of surgery) with tumor in place;
- Measurable disease based on RECIST 1.1;
- 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
- Calculated creatinine clearance \> 30 ml/min using MDRD formula;
- Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before inclusion:
- Potassium
- Magnesium
- Total Calcium (corrected for serum albumin);
- 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;
- Patients having taken cognizance of the information sheet and having signed the informed consent;
- Patients covered by medical insurance.
- Must be able to swallow ribociclib;
- Subjects must be able to communicate with the investigator and comply with the requirements of the study procedures;
- Must be willing to remain at the clinical site as required by the protocol.
- Patient eligible to resection surgery after 3 cycles of Ribociclib;
- Patient eligible to neoadjuvant chemotherapy;
- Concomitant bilateral breast cancer;
- 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, Ribobociblib or radiotherapy;
- 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
- Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
- Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study drug)
- Inability to determine the QTcF interval
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- Systolic Blood Pressure (SBP) \>160 or \<90 mmHg
- Severe dementia;
- Patients unable to express their consent;
- Vulnerable persons as defined by article L1121-5 - 8:
- 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;
- Persons admitted to a social or health facility for reasons other than research;
- Adults subject to a legal protection order or unable to give their consent.
- Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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 (CALHYS)
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.
- Being tested
- Ribociclib Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ribociclib Oral TabletDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Ribociclib Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Phase II : at 24-months
Secondary outcomes (16)
overall survival
Evaluate overall survival (OS)
Measured: 24 months
overall survival
Evaluate overall survival (OS)
Measured: 60 months
progression free survival
Evaluate progression free survival (PFS)
Measured: 24 months
progression free survival
Evaluate progression free survival (PFS)
Measured: 60 months
quality of Life (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30)
Evaluate quality of Life (items values from 1 to 4 per question)
Measured: 60 months
quality of Life (ELDERLY CANCER PATIENTS14)
Evaluate quality of Life (items values from 1 to 4 per question)
Measured: 60 months
compliance to Ribociclib
The treatment compliance will be assessed with the 8-item Morisky Medication Adherence Scale (score from 0 to 8)
Measured: 24 months
medical health status
Evaluate the medical health status of the patients with the questionnaire G8, clinical score and visual analog scale for pain severity measurement (score from 0 to 17)
Measured: 60 months
psychosocial health status
Evaluate the psychosocial status of the patients with GDS 4 questionnaire (score from 0 to 4)
Measured: 60 months
functional health status
Evaluate the functional status of the patients with the questionnaires MINI MENTAL STATE EXAMINATION (score from 0 to 30)
Measured: 60 months
functional health status
Evaluate the functional status of the patients with the questionnaires Autonomy Daily Living (score from 0 to 6)
Measured: 60 months
functional health status
Evaluate the functional status of the patients with the questionnaires (Instrumental Activities in Daily Living (score from 0 to 8)
Measured: 60 months
functional health status
Evaluate the functional status of the patients with the questionnaires walking speed
Measured: 60 months
functional health status
Evaluate the functional status of the patients with the questionnaires percentage of weight loss
Measured: 60 months
functional health status
Evaluate the functional status of the patients with Handgrip strength evaluation
Measured: 60 months
overall tolerance of ribociclib using V5.0 Common Terminology Criteria for Adverse Events scale
The overall tolerance of Ribociclib during ribociclib monotherapy treatment and concomitant ribociclib radiotherapy treatment will be evaluated using clinical and biological assessment and graded according to the V5.0 scale.
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2022
- Study start26 Jun 2023
- Primary completion26 Mar 2026
- Study completion26 Mar 2026
Why it stopped: Sponsor decision due to recruitment default
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 Negative Breast Cancer Not Immediately OperatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- step 1 : 600mg of ribociclib step 2 : 400mg of ribociclib step 3 : 200mg of ribociclib
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Antoine Lacassagne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664893
- Sponsor's protocol ID
- 2017/78
- Acronym
- CALHYS
- Status last verified
- Apr 2026
- First submitted
- 25 Nov 2022
- Last updated
- 15 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 (CALHYS)
- ClinicalTrials.gov ID
- NCT05664893
- Acronym / sponsor ID
- CALHYS / 2017/78
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision due to recruitment default
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre Antoine LacassagneUniversity, hospital or other
- Study start
- 26 Jun 2023 (actual)
- Primary completion
- 26 Mar 2026 (actual)
- Study completion
- 26 Mar 2026 (actual)
- First posted
- 27 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- step 1 : 600mg of ribociclib step 2 : 400mg of ribociclib step 3 : 200mg of ribociclib
| Arm | Type | Receives |
|---|---|---|
| Principal arm | Experimental | Drug: Ribociclib Oral Tabletregistration 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 |
Who may qualify
- Ages
- 70 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (81 listed)
- 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;
- Previous treatment, in the 2 years before inclusion, by chemotherapy, hormone therapy (more than 6 months before study registration), thoracic surgery or radiotherapy for a malignant tumor;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ribociclib Oral Tablet600mg 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 | Drug | Principal arm |
Primary outcome
Phase I : determination of Maximal Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) of Ribociclib
Time frame: 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 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 II : evaluation of the efficacy of Ribociclib in association with hormone therapy and hypofractionated radiotherapy
Time frame: Phase II : at 24-months
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.
16 secondary outcomes
overall survival
Time frame: 24 months
overall survival
Time frame: 60 months
progression free survival
Time frame: 24 months
progression free survival
Time frame: 60 months
quality of Life (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30)
Time frame: 60 months
quality of Life (ELDERLY CANCER PATIENTS14)
Time frame: 60 months
compliance to Ribociclib
Time frame: 24 months
medical health status
Time frame: 60 months
psychosocial health status
Time frame: 60 months
functional health status
Time frame: 60 months
functional health status
Time frame: 60 months
functional health status
Time frame: 60 months
functional health status
Time frame: 60 months
functional health status
Time frame: 60 months
functional health status
Time frame: 60 months
overall tolerance of ribociclib using V5.0 Common Terminology Criteria for Adverse Events scale
Time frame: 25 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ribociclib Oral Tablet in people with HER2 Negative Breast Cancer Not Immediately Operated, run by Centre Antoine Lacassagne at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 81 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I : determination of Maximal Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) of Ribociclib (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.