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

NCT03447132 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: ICRG1201
• Study Type: interventional
• Target: 354
• Locations: 8 countries
• Sites: 14

Brief 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 breast cancer. Eligible patients will be assessed upfront using the OncotypeDX® molecular test (Recurrence Score \<31).

Conditions

Breast Neoplasm Female

Keywords

Breast Cancer; Luminal; Neoadjuvant; pCR; Surgery

Outcome Measures

Primary Outcomes (1)

• pCR according to Le Chevalier's classification

  pathological complete response will be assessed according to Le Chevalier's classification between two arms

  up to 5 years after the end of treatment period

Secondary Outcomes (5)

• pCR according to Sataloff's classification

  up to 5 years after the end of treatment period

• radiological response

  up to 5 years after the end of treatment period

• Rate of breast conservative surgery

  up to 5 years after the end of treatment period

• Safety /Tolerability of the combination Fulvestrant + Palbociclib

  up to 5 years after the end of treatment period

• DFS and OS

  up to 5 years after the end of treatment period

Study Arms (2)

Fulvestrant 500mg + Palbociclib 125mg

ACTIVE COMPARATOR

\+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months

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

Drug: Fulvestrant 500mg; Drug: Goserelin 3.6 MG; Drug: Placebos

Interventions

Fulvestrant 500mg DRUG

All patients in all arms will receive Fulvestrant 500mg

Fulvestrant 500mg + Palbociclib 125mg; Fulvestrant 500mg + Placebos

Palbociclib 125mg DRUG

Dose reduction to 100 mg and 75 mg

Fulvestrant 500mg + Palbociclib 125mg

Goserelin 3.6 MG DRUG

Only for pre or peri menopausal patient

Fulvestrant 500mg + Palbociclib 125mg; Fulvestrant 500mg + Placebos

Placebos DRUG

Placebo

Fulvestrant 500mg + Placebos

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Hematology:
• Neutrophil count ≥ 1.5 G/L.
• Platelet count ≥ 100 G/L.
• Leucocyte count \> 3.0 G/L.
• Hb\> 9g/dl.

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• International Cancer Research Group, United Arab Emirates: lead
• AstraZeneca: collaborator
• Pfizer: collaborator
• Genomic Health®, Inc.: collaborator

Study Sites (14)

Center Pierre et Marie Curie

Algiers, Algeria

Location

Cancer Center - Blida

Blida, Algeria

Location

CHU - Oran

Oran, Algeria

Location

University of Alexandria

Alexandria, Egypt

Location

National Cancer Institut (NCI)

Cairo, Egypt

Location

King Hussein Cancer Center (KHCC) - Amman

Amman, Jordan

Location

Hotel Dieu de France

Beirut, Lebanon

Location

Hopital Cheikh Khalifa Ibn Zaid

Casablanca, Morocco

Location

Department of Oncology - Institut National d'Oncologie

Rabat, Morocco

Location

King Abdul Aziz Medical City-National Guard Health Affairs (NGHA)

Riyadh, Saudi Arabia

Location

Oncology Center- King Fahad Medical City (KFMC)

Riyadh, Saudi Arabia

Location

Oncology Center- King Saud University Medical City (KSUMC)

Riyadh, Saudi Arabia

Location

Oncologie Medicale de l'Ariana (SOMA)

Tunis, Tunisia

Location

Tawam Hospital

Al Ain City, United Arab Emirates

Location

Related Publications (1)

• 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.

  PMID: 36680581 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; palbociclib; Goserelin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Jean-Marc Nabholtz, MD

  International Cancer Research Group

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2018
• First Posted: February 27, 2018
• Study Start: December 20, 2017
• Primary Completion: April 12, 2021
• Study Completion: July 20, 2021
• Last Updated: March 10, 2023

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share

Locations

AE (1); AL (3); JO (1); EG (2); LE (1); MO (2); TU (1); SA (3)