Breast Neoplasm FemalePhase 3SAFIANCT03447132
Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant
A Phase 3 study testing Fulvestrant 500mg, Palbociclib 125mg and Goserelin 3.6 MG in people with Breast Neoplasm Female, run by International Cancer Research Group, United Arab Emirates at 14 sites in 8 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Female
- What is being tested?
- Fulvestrant 500mg, Palbociclib 125mg and Goserelin 3.6 MG
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 354 participants
- Where
- 14 sitesin 8 countries
- Study dates
- 20 Dec 2017to 20 Jul 2021
- Phase
- Phase 3
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
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- 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.
- Hematology:
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
14 sites in 8 countries.
14 sites in 8 countries
Algeria3 sites
Center Pierre et Marie Curie
Algiers
Cancer Center - Blida
Blida
CHU - Oran
Oran
Saudi Arabia3 sites
King Abdul Aziz Medical City-National Guard Health Affairs (NGHA)
Riyadh
Oncology Center- King Fahad Medical City (KFMC)
Riyadh
Oncology Center- King Saud University Medical City (KSUMC)
Riyadh
Egypt2 sites
University of Alexandria
Alexandria
National Cancer Institut (NCI)
Cairo
Morocco2 sites
Hopital Cheikh Khalifa Ibn Zaid
Casablanca
Department of Oncology - Institut National d'Oncologie
Rabat
About this study
Official 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®
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).
Read the detailed description
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 or
- 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.
- Conditions
- Breast Neoplasm Female
- Being tested
- Fulvestrant 500mg, Palbociclib 125mg, Goserelin 3.6 MG, Placebos
- Keywords
- Breast Cancer, Luminal, Neoadjuvant, pCR, Surgery
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fulvestrant 500mgDrug
All patients in all arms will receive Fulvestrant 500mg
Palbociclib 125mgDrug
Dose reduction to 100 mg and 75 mg
Goserelin 3.6 MGDrug
Only for pre or peri menopausal patient
PlacebosDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Fulvestrant 500mg + Palbociclib 125mg | Active comparator | + Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months Receives: Drug: Fulvestrant 500mg; Drug: Palbociclib 125mg; Drug: Goserelin 3.6 MG |
| Fulvestrant 500mg + Placebos | Placebo comparator | + Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months Receives: Drug: Fulvestrant 500mg; Drug: Goserelin 3.6 MG; Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR according to Le Chevalier's classification
pathological complete response will be assessed according to Le Chevalier's classification between two arms
Measured: up to 5 years after the end of treatment period
Secondary outcomes (5)
pCR according to Sataloff's classification
pathological complete response will be assessed according to Sataloff's classification between two arms
Measured: up to 5 years after the end of treatment period
radiological response
radiological response according to the WHO criteria (US/Mammography/MRI)
Measured: up to 5 years after the end of treatment period
Rate of breast conservative surgery
Rate of breast conservative surgery will be assessed and compared between two arms
Measured: up to 5 years after the end of treatment period
Safety /Tolerability of the combination Fulvestrant + Palbociclib
Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs. Treatment-related adverse events will be assessed by using CTCAE v4.1 classification
Measured: up to 5 years after the end of treatment period
DFS and OS
Evaluation and comparison of Disease Free Survival (DFS) and Overall Survival (OS) between two arms
Measured: up to 5 years after the end of treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2018
- Study start20 Dec 2017
- Primary completion12 Apr 2021
- Study completion20 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast Neoplasm FemaleStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 354 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Cancer Research Group, United Arab Emirates
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Pfizer, Genomic Health®, Inc.
- Responsible party
- Sponsor
- Investigators
- Jean-Marc Nabholtz, MD, Study chair, International Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03447132
- Sponsor's protocol ID
- ICRG1201
- Acronym
- SAFIA
- Status last verified
- Nov 2018
- First submitted
- 11 Feb 2018
- Last updated
- 10 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Alsaleh K, Al Zahwahry H, Bounedjar A, Oukkal M, Saadeddine A, Mahfouf H, Bouzid K, Bensalem A, Filali T, Abdel-Razeq H, Larbaoui B, Kandil A, Abulkhair O, Al Foheidi M, Ghosn M, Rasool H, Boussen H, Mezlini A, Haddaoui A, Ayari J, Al Ghamdi M, Errihani H, Abdel-Aziz N, Arafah M, Dabouz F, Bahadoor M, Kullab S, Nabholtz JM; King Saud University, Riyadh, Kingdom of Saudi Arabia, and the International Cancer Research Group (ICRG), Sharjah, Unites Arab Emirates. Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial. J Cancer Res Clin Oncol. 2023 Aug;149(9):6171-6179. doi: 10.1007/s00432-023-04588-3. Epub 2023 Jan 21.
PubMed 36680581
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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®
- ClinicalTrials.gov ID
- NCT03447132
- Acronym / sponsor ID
- SAFIA / ICRG1201
- Conditions
- Breast Neoplasm Female
- Keywords
- Breast Cancer, Luminal, Neoadjuvant, pCR, Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 354 participants (actual)
- Lead sponsor
- International Cancer Research Group, United Arab EmiratesUniversity, hospital or other
- Collaborators
- AstraZeneca, Pfizer, Genomic Health®, Inc.
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 12 Apr 2021 (actual)
- Study completion
- 20 Jul 2021 (actual)
- First posted
- 27 Feb 2018 (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.
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).
Detailed description
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 or
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fulvestrant 500mg + Palbociclib 125mg | Active comparator | Drug: Fulvestrant 500mg, Drug: Palbociclib 125mg, Drug: Goserelin 3.6 MG+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months |
| Fulvestrant 500mg + Placebos | Placebo comparator | Drug: Fulvestrant 500mg, Drug: Goserelin 3.6 MG, Drug: Placebos+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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)
Key exclusion criteria (21 listed)
- 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).
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 |
|---|---|---|
| Fulvestrant 500mgAll patients in all arms will receive Fulvestrant 500mg | Drug | Fulvestrant 500mg + Palbociclib 125mg, Fulvestrant 500mg + Placebos |
| Palbociclib 125mgDose reduction to 100 mg and 75 mg | Drug | Fulvestrant 500mg + Palbociclib 125mg |
| Goserelin 3.6 MGOnly for pre or peri menopausal patient | Drug | Fulvestrant 500mg + Palbociclib 125mg, Fulvestrant 500mg + Placebos |
| PlacebosPlacebo | Drug | Fulvestrant 500mg + Placebos |
Primary outcome
pCR according to Le Chevalier's classification
Time frame: up to 5 years after the end of treatment period
pathological complete response will be assessed according to Le Chevalier's classification between two arms
5 secondary outcomes
pCR according to Sataloff's classification
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
Rate of breast conservative surgery
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
DFS and OS
Time frame: up to 5 years after the end of treatment period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
- Results publication: PubMed 36680581Alsaleh K, Al Zahwahry H, Bounedjar A, Oukkal M, Saadeddine A, Mahfouf H, Bouzid K, Bensalem A, Filali T, Abdel-Razeq H, Larbaoui B, Kandil A, Abulkhair O, Al Foheidi M, Ghosn M, Rasool H, Boussen H, Mezlini A, Haddaoui A, Ayari J, Al Ghamdi M, Errihani H, Abdel-Aziz N, Arafah M, Dabouz F, Bahadoor M, Kullab S, Nabholtz JM; King Saud University, Riyadh, Kingdom of Saudi Arabia, and the International Cancer Research Group (ICRG), Sharjah, Unites Arab Emirates. Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial. J Cancer Res Clin Oncol. 2023 Aug;149(9):6171-6179. doi: 10.1007/s00432-023-04588-3. Epub 2023 Jan 21.
- Individual participant dataSharing planned: Yes
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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.
Jean-Marc Nabholtz, MD study chair
International Cancer Research Group
14 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fulvestrant 500mg, Palbociclib 125mg and Goserelin 3.6 MG in people with Breast Neoplasm Female, run by International Cancer Research Group, United Arab Emirates at 14 sites in 8 countries.
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 28 inclusion and 21 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: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Algeria, Saudi Arabia, Egypt, Morocco, Jordan and 3 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
pCR according to Le Chevalier's classification (time frame: up to 5 years after the end of treatment period). 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 NCT03447132, which also lists 1 linked publication.
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 10 Mar 2023.