Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant (SAFIA)

  • End date
    Sep 1, 2023
  • participants needed
  • sponsor
    International Cancer Research Group, United Arab Emirates
Updated on 27 February 2022
platelet count
renal function
breast cancer
endocrine therapy
white blood cells
neutrophil count
adjuvant therapy
cancer treatment
serum calcium
goserelin 3.6 mg
palbociclib 125 mg


This is a multicenter, international, double-blind randomized Phase III study to evaluate the pathological complete response (pCR) according to Chevalier classification between Fulvestrant and the combination of Fulvestrant plus Palbociclib as neoadjuvant therapy of hormone-sensitive patients with operable luminal breast cancer.

Eligible patients will be assessed upfront using the OncotypeDX molecular test (Recurrence Score <31).


This is a multicenter, international, double-blind, randomized study.

Eligible patients based on inclusion/exclusion criteria will be assessed using OncotypeDX molecular test. Patients with low/intermediate risk (Recurrence Score <31) will be treated with the induction neoadjuvant Fulvestrant (500 mg (milligram) intra muscular(i.m) at Day 1, 14 and 28 and then every 4 weeks), plus Goserelin (3.6 mg subcutaneous (s.c) every 4 weeks, only for pre and peri-menopausal patients) for 4 months, followed by clinical and radiological assessment of the disease response.

Patients with objective response or stabilization will be randomized and treated for 4 additional months with:

  • Fulvestrant 500 mg i.m every 4 weeks (+ Goserelin 3.6 mg s.c every 4 weeks, only for pre and peri-menopausal patients) and Placebo


  • Combination Fulvestrant 500 mg i.m every 4 weeks (+ Goserelin 3.6 mg s.c every 4 weeks, only for pre and peri-menopausal patients) and Palbociclib 125 mg per os daily, 3 weeks on and 1 week off.

Patients with documented progressive disease will be considered at the discretion of the investigator for surgery or neoadjuvant chemotherapy. The preferred chemotherapy protocol will be FEC 100 -Taxotere (5fluorouracil 500mg/m2, Epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 (FEC) q3 weeks for 3 cycles followed by Docetaxel 100 mg/m2 (T) q 3 weeks for 3 cycles) for a total of 6 cycles with clinical and radiological assessment after each 3 cycles of chemotherapy (CT). Chemotherapy candidates will as well undergo surgery. The expected interval between the cycles will be 21 days, unless the patient has not recovered from toxicity. Specific dose adjustments will be set out in the protocol.

Breast and nodal surgery will be performed at completion of therapy (8 months of hormonal therapy for responding patients and 6 additional cycles of CT for non-responders). The type of surgery will be left at the discretion of the investigators.

Radiation therapy and adjuvant systemic treatment and endocrine therapy will be as well left at the discretion of the investigators.

Patients will be followed every 6 months during 5 years post surgery.

Condition Breast Neoplasm Female
Treatment placebos, Palbociclib 125mg, Fulvestrant 500mg, Goserelin 3.6 MG
Clinical Study IdentifierNCT03447132
SponsorInternational Cancer Research Group, United Arab Emirates
Last Modified on27 February 2022


Yes No Not Sure

Inclusion Criteria

Written informed consent prior to beginning specific protocol procedures including expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to the local regulatory requirements
Age >18\
Postmenopausal women or pre-menopausal (with medical or surgical oophorectomy)
Performance status < 2 (according to WHO criteria)
Histologically confirmed non-metastatic breast cancer (Luminal A or B)
HR (hormone receptor ) positive (Estrogen or Progesterone)> 1%
Her-2 negative (score 0 or 1 by immunochemistry), FISH (fluorescence in situ hybridization) negative if IHC (immuno-histochemistry) score 2)
Clinical stage II and IIIa
No previous breast cancer treatment by surgery, radiotherapy, hormone therapy or chemotherapy
Measurable or evaluable disease
Neutrophil count 1.5 G/L
Platelet count 100 G/L
Leucocyte count > 3.0 G/L
Hb> 9g/dl
Hepatic function
Total bilirubin 1.5 time the Upper Normal Limit (UNL)
ASAT (alanine aminotransferase aspartate transaminase ) 2.5xUNL
ALAT (alanine aminotransferase) 2.5xUNL
Alkaline phosphatase 2.5 time the upper normal limit (UNL)
Renal function
Serum creatinine 1.5xUNL (and if Serum creatinine >1.5xUNL, creatinine clearance 50 mL/min)
Creatinine clearance 40 mL/min in case of MRI
Metabolic function
Serum magnesium lower limit of normal
Serum calcium lower limit of normal
No progressive heart disease and no anthracycline contraindication (normal LVEF ( left ventricular ejection fraction) according to the institution guidelines)
Negative pregnancy test (urine or serum) within 7 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment

Exclusion Criteria

Male patients
Her-2 positive tumors or unknown HR/Her-2 status
Pregnancy or breast-feeding, or plan to become pregnant within 6 months post treatment
No willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months post treatment
Any form of breast cancer other than those described in the inclusion criteria, particularly inflammatory and/or overlooked forms (stages IIIb or IV)
Non-measurable tumour
Bilateral breast cancer
Previous treatment for breast cancer including surgery for their disease or have had primary axillary dissection, radiotherapy and systemic therapy
Patient with history of other cancer, except in situ cervical cancer or baso-cellular skin cancer, considered cured
Patient has another disease, which is deemed incompatible with the inclusion in the protocol
Heart, kidney, medullary, respiratory or liver failure. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year before enrollment in the study
History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease at baseline
Acute urinary infection, ongoing hemorrhagic cystitis
Uncontrolled diabetes
Symptomatic or progressive disorder of the central nervous system (CNS) Peripheral neuropathy > grade 2
Significant psychiatric abnormalities
History of hypersensitivity to studied treatment or excipients
Known previous or ongoing abuse narcotic drug, other medication or alcohol
Any investigational agent within 30 days before initiation of study treatment
No major surgical procedure within 28 days of initiation of treatment
Subject unwilling or unable to comply with study requirement
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