Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant

• Register: ClinicalTrials.gov
• Last refreshed on: 20 March 2023
• Main ID: NCT03447132
• Date of registration: 11/02/2018
• Prospective Registration: No
• Primary sponsor: International Cancer Research Group, United Arab Emirates
• Public title: Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant SAFIA
• Scientific title: Multicentre, International Neoadjuvant Randomized Double-blind Trial Comparing Fulvestrant® to a Combination of Fulvestrant® and Palbociclib (CDK 4/6 Inhibitor) in Patients With Operable Luminal Breast Cancer Responding to Fulvestrant®
• Date of first enrolment: December 20, 2017
• Target sample size: 354
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03447132
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Algeria, Egypt, Jordan, Lebanon, Morocco, Saudi Arabia, Tunisia, United Arab Emirates

Contacts

• Name: Jean-Marc Nabholtz, MD
• Affiliation: International Cancer Research Group

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 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.

2. Age >18.

3. Postmenopausal women or pre-menopausal (with medical or surgical oophorectomy)

4. Performance status < 2 (according to WHO criteria).

5. 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).

6. Clinical stage II and IIIa.

7. No previous breast cancer treatment by surgery, radiotherapy, hormone therapy or
chemotherapy.

8. Measurable or evaluable disease.

9. Hematology:

- Neutrophil count = 1.5 G/L.

- Platelet count = 100 G/L.

- Leucocyte count > 3.0 G/L.

- Hb> 9g/dl.

10. 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).

11. 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.

12. Metabolic function:

- Serum magnesium = lower limit of normal.

- Serum calcium = lower limit of normal.

13. No progressive heart disease and no anthracycline contraindication (normal LVEF ( left
ventricular ejection fraction) according to the institution guidelines).

14. 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:

1. Male patients.

2. Her-2 positive tumors or unknown HR/Her-2 status.

3. Pregnancy or breast-feeding, or plan to become pregnant within 6 months post
treatment.

4. No willingness to use highly effective methods of contraception (per institutional
standard) during treatment and for 6 months post treatment.

5. Any form of breast cancer other than those described in the inclusion criteria,
particularly inflammatory and/or overlooked forms (stages IIIb or IV).

6. Non-measurable tumour.

7. Bilateral breast cancer.

8. Previous treatment for breast cancer including surgery for their disease or have had
primary axillary dissection, radiotherapy and systemic therapy.

9. Patient with history of other cancer, except in situ cervical cancer or baso-cellular
skin cancer, considered cured.

10. Patient has another disease, which is deemed incompatible with the inclusion in the
protocol.

11. 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.

12. Uncontrolled diabetes.

13. Symptomatic or progressive disorder of the central nervous system (CNS) Peripheral
neuropathy > grade 2

14. Significant psychiatric abnormalities.

15. History of hypersensitivity to studied treatment or excipients

16. Known previous or ongoing abuse narcotic drug, other medication or alcohol

17. Any investigational agent within 30 days before initiation of study treatment.

18. No major surgical procedure within 28 days of initiation of treatment.

19. Subject unwilling or unable to comply with study requirement.



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Breast Neoplasm Female

Intervention(s)

Drug: Goserelin 3.6 MG

Drug: Placebos

Drug: Fulvestrant 500mg

Drug: Palbociclib 125mg

Primary Outcome(s)

pCR according to Le Chevalier's classification [Time Frame: up to 5 years after the end of treatment period]

Secondary Outcome(s)

pCR according to Sataloff's classification [Time Frame: up to 5 years after the end of treatment period]

DFS and OS [Time Frame: up to 5 years after the end of treatment period]

radiological response [Time Frame: up to 5 years after the end of treatment period]

Safety /Tolerability of the combination Fulvestrant + Palbociclib [Time Frame: up to 5 years after the end of treatment period]

Rate of breast conservative surgery [Time Frame: up to 5 years after the end of treatment period]

Secondary ID(s)

ICRG1201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

AstraZeneca

Genomic Health®, Inc.

Pfizer