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Breast CancerPhase 2FACILENCT03944434

FACILE: FeAsibility of First-line RiboCIclib in OLdEr Patients with Advanced Breast Cancer

A Phase 2 study testing Ribociclib, Aromatase Inhibitors, non steroideal and LHRH agonist in people with Breast Cancer, run by Fondazione Sandro Pitigliani at 1 site in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Phase II, multicenter, single arm trial to assess the feasibility of first line ribociclib in combination with a non steroidal aromatase inhibitor in women or men aged 70 years-old or older, with hormone receptor positive/HER2 negative advanced breast cancer Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Ribociclib, Aromatase Inhibitors, non steroideal and LHRH agonist
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
1 siteItaly
Study dates
27 Dec 2018to 27 Nov 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

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
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Patients male or female, aged 70 years-old or older at the time of informed consent.
  • Patients with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
  • Measurable or not measurable but evaluable disease according to RECIST criteria 1.1
  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
  • Patient has a HER2 negative breast cancer 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.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
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  • Patient has an estimated life expectancy of > 24 weeks.
  • Patient has adequate bone marrow and organ function as defined by all of the following laboratory values (as assessed by local laboratory):
  • Absolute neutrophil count ≥1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hemoglobin ≥ 9.0 g/dL
  • Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
  • INR ≤ 1.5
  • Serum creatinine <1.5 mg/dl or creatinine clearance ≥50mL/min
  • Total bilirubin < ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN.
  • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be < 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN.
  • Patient must have a 12-lead ECG values with all of the following parameters at screening:
  • QTcF interval at screening < 450 msec (using Fridericia's correction)
  • Resting heart rate ≥50 bpm
  • Patient must be able to swallow ribociclib and NSAI tablets
  • Written informed consent must be obtained prior to any screening procedures
  • Patient must be able to communicate with the investigator and comply with the requirements of the study procedures.

Who cannot join

  • 1. Patient has received prior treatment with chemotherapy or hormonal therapy (except for neoadjuvant/ adjuvant chemotherapy), or any CDK4/6 inhibitor.
  • NOTE:
  • Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
  • Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
  • 2. Patient has a known hypersensitivity to any of the excipients of ribociclib or NSAI 3. Patient in concurrently using other anti-cancer therapy. 4. Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 5.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
  • 5. Patient who has received extended-field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to start of treatment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patient from whom ≥ 25% of the bone marrow has been previously irradiated are also excluded 6. Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
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  • 7. Patient with central nervous system (CNS) metastases unless they meet all of the following criteria:
  • At least 4 weeks from prior therapy for CNS disease completion (including radiation and/or surgery) to starting the study treatment.
  • Clinically stable CNS lesions at the time of study treatment initiation and not receiving steroids and/or enzyme-inducing anti-epileptic medications for the management of brain metastases for at least 2 weeks.
  • 8. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • 9. Patient has a known history of HIV infection (testing not mandatory). 10. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgement, 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.) 11. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
  • <!-- -->
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • 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)
  • 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 hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. 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 (within 5 half-lives or 7 days prior to starting study drug) iii. Inability to determine the QTcF interval on screening f. Systolic Blood Pressure (SBP) >160 or <90 mmHg 12. Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
  • Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummeloes, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of CYP3A4/5,
  • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
  • 13. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
  • NOTE:
  • The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Hospital of Prato

    Prato, Italy, 59100

Other trials in Italy

About this study

Official title: Phase II, Multicenter, Single Arm Trial to Assess the Feasibility of First Line Ribociclib in Combination with a Non Steroidal Aromatase Inhibitor in Elderly Patients with Hormone Receptor Positive/HER2 Negative Advanced Breast Cancer

Phase II, multicenter, single arm trial to assess the feasibility of first line ribociclib in combination with a non steroidal aromatase inhibitor in women or men aged 70 years-old or older, with hormone receptor positive/HER2 negative advanced breast cancer

Read the detailed description

Elderly patients are generally more susceptible to the side effects of active treatments. Patients entered in clinical trials, especially the elderly, are not completely representative of the "real" population because of selection process. The lack of data collected from a real population turns the indication of treatment a challenging task and expose older patients to a risk of under treatment (fear of excessive toxicity because of the lack of data).

With the aim of covering this gap, we are planning to run a phase II trial evaluating the feasibility of delivering the combination of ribociclib plus NSAI as first-line treatment specifically in a population of breast cancer patients aged ≥70 years.

Primary endpoint:

  • The treatment feasibility will be evaluated as the proportion of patients not having experienced disease progression (PD), still on treatment with ribociclib plus NSAI 6 months after the first drug administration

Secondary endpoints:

  • Treatment adherence
  • Safety and tolerability
  • Patient reported outcomes (PROs)
  • Overall response rate (ORR)
  • Progression free survival (PFS)
Conditions
Breast Cancer
Being tested
Ribociclib, Aromatase Inhibitors, non steroideal, LHRH agonist
Keywords
ribociclib, hormone receptor positive
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RibociclibDrug

    Also called Kisqali

    ribociclib 600 mg/day orally

  • Aromatase Inhibitors, non steroidealDrug

    Also called Femara, Arimidex

    letrozole 2.5 mg/day orally or anastrozole 1 mg/day orally

  • LHRH agonistDrug

    Also called Triptorelin, Leuprolide, Goserelin

    Triptorelin 3,75 mg or Leuprolide 3,75 mg or goserelin 3,6 mg, as injectable.

Study groups in NCT03944434
Study groupRoleWhat they receive
single armExperimentalpatients will receive anastrozole tablets (1 mg once daily) or letrozole tablets (2.5 mg once daily) + ribociclib tablets (600 mg day 1 to 21 in a 28 day cycle). Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, physician's decision, patient's refusal/consent withdrawal, or lost to follow-up. A LHRH agonist (triptorelin 3,75 mg or leuprolide 3,75 mg or goserelin 3,6 mg, as injectable intramuscular (i.m.) or subcutaneous (s.c.) implant every 28 days) will be used in men.
Receives: Drug: Ribociclib; Drug: Aromatase Inhibitors, non steroideal; Drug: LHRH agonist

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment feasibility

    The treatment feasibility will be evaluated as the proportion of patients not having experienced disease progression (PD), still on treatment with ribociclib plus NSAI 6 months after the first drug administration

    Measured: 6 months

Secondary outcomes (6)

  1. Patient Diary

    Diary to self-report data regarding taking medication and to evaluate treatment adherence

    Measured: 36 months

  2. Incidence of Treatment-Emergent adverse events and serious adverse events (Safety and tolerability)

    Adverse events (AE), AE of special interest and serious adverse events (SAE). CTCAE V. 5.0 will be adopted.

    Measured: 36 months

  3. Patient reported outcomes (PROs)

    PROs using Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire, score: 0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much;

    Measured: 36 months

  4. Overall response rate (ORR)

    ORR as defined by RECIST 1.1 for patients with measurable disease

    Measured: 36 months

  5. Progression free survival (PFS)

    PFS as defined by RECIST 1.1 based on investigator' assessment

    Measured: 36 months

  6. Number of comorbities (impact on study inclusion)

    Number of comorbidities and relative grading will be collected using Cumulative Illness Rating Scale- Geriatric (CIRS-G) (for patients not included into the study due to comorbities).SCORE: 0- No problem , 1- Current mild problem or past significant problem, 2- Moderate disability or morbidity/requires first line therapy, 3- Severe/ constant significant disability/ uncontrollable chronic problems, 4- Extremely severe/ immediate treatment required/ end organ failure/ severe impairment in function

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2019
  2. Study start27 Dec 2018
  3. Primary completion27 Dec 2024
  4. Study completion27 Nov 2025 (estimated)

Resources

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 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
116 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03944434
Sponsor's protocol ID
FACILE
Acronym
FACILE
Status last verified
Feb 2025
First submitted
9 Apr 2019
Last updated
26 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.

    PubMed 25524798

  • Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Dieras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303.

    PubMed 27959613

  • Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, Andre F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. doi: 10.1056/NEJMoa1609709. Epub 2016 Oct 7.

    PubMed 27717303

  • Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Tredan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. doi: 10.1200/JCO.2017.75.6155. Epub 2017 Oct 2.

    PubMed 28968163

  • Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018 Jul 1;29(7):1541-1547. doi: 10.1093/annonc/mdy155.

    PubMed 29718092

  • Rugo HS, Turner NC, Finn RS, Joy AA, Verma S, Harbeck N, Masuda N, Im SA, Huang X, Kim S, Sun W, Iyer S, Schnell P, Bartlett CH, Johnston S. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018 Sep;101:123-133. doi: 10.1016/j.ejca.2018.05.017. Epub 2018 Jul 25.

    PubMed 30053671

  • Sonke GS, Hart LL, Campone M, Erdkamp F, Janni W, Verma S, Villanueva C, Jakobsen E, Alba E, Wist E, Favret AM, Bachelot T, Hegg R, Wheatley-Price P, Souami F, Sutradhar S, Miller M, Germa C, Burris HA. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial. Breast Cancer Res Treat. 2018 Feb;167(3):659-669. doi: 10.1007/s10549-017-4523-y. Epub 2017 Oct 22.

    PubMed 29058175

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ribociclib, Aromatase Inhibitors, non steroideal and LHRH agonist in people with Breast Cancer, run by Fondazione Sandro Pitigliani at 1 site in Italy.

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 22 inclusion and 23 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: under way, not looking for participants, as of the sponsor's last update on 26 Feb 2025. 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 Italy. 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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?

Treatment feasibility (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03944434, which also lists 7 linked publications.

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 26 Feb 2025.

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