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

NCT03944434 | Active Not Recruiting Phase 2

• 1 other identifier: FACILE
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Breast Cancer

Keywords

ribociclib; hormone receptor positive

Outcome Measures

Primary Outcomes (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

  6 months

Secondary Outcomes (6)

• Patient Diary

  36 months

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

  36 months

• Patient reported outcomes (PROs)

  36 months

• Overall response rate (ORR)

  36 months

• Progression free survival (PFS)

  36 months

Study Arms (1)

single arm

EXPERIMENTAL

patients 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.

Drug: Ribociclib; Drug: Aromatase Inhibitors, non steroideal; Drug: LHRH agonist

Interventions

Ribociclib DRUG

ribociclib 600 mg/day orally

Also known as: Kisqali

single arm

Aromatase Inhibitors, non steroideal DRUG

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

Also known as: Femara, Arimidex

single arm

LHRH agonist DRUG

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

Also known as: Triptorelin, Leuprolide, Goserelin

single arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• \. 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.
• \. 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).
• \. 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.
• \. 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.
• \. 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).
• \. 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:
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• 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)

Sponsors & Collaborators

• Fondazione Sandro Pitigliani: lead
• Novartis: collaborator

Study Sites (1)

Hospital of Prato

Prato, Italy, 59100, Italy

Location

Related Publications (7)

• 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.

  PMID: 25524798 BACKGROUND

• 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.

  PMID: 27959613 BACKGROUND

• 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.

  PMID: 27717303 BACKGROUND

• 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.

  PMID: 28968163 BACKGROUND

• 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.

  PMID: 29718092 BACKGROUND

• 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.

  PMID: 30053671 BACKGROUND

• 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.

  PMID: 29058175 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Aromatase Inhibitors; Letrozole; Anastrozole; Gonadotropin-Releasing Hormone; Triptorelin Pamoate; Leuprolide; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Laura Biganzoli, MD

  Hospital of Prato

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: May 9, 2019
• Study Start: December 27, 2018
• Primary Completion: December 27, 2024
• Study Completion: November 27, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)