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®
Overview
- Phase
- Phase 3
- Intervention
- Palbociclib 125mg
- Conditions
- Breast Neoplasm Female
- Sponsor
- International Cancer Research Group, United Arab Emirates
- Enrollment
- 354
- Locations
- 14
- Primary Endpoint
- pCR according to Le Chevalier's classification
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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).
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.
Investigators
Eligibility Criteria
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.
- •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:
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.
Arms & Interventions
Fulvestrant 500mg + Palbociclib 125mg
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Palbociclib 125mg
Fulvestrant 500mg + Palbociclib 125mg
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Fulvestrant 500mg
Fulvestrant 500mg + Palbociclib 125mg
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Goserelin 3.6 MG
Fulvestrant 500mg + Placebos
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Fulvestrant 500mg
Fulvestrant 500mg + Placebos
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Goserelin 3.6 MG
Fulvestrant 500mg + Placebos
+ Goserelin 3.6 mg if pre or peri menopausal patient - duration 4 months
Intervention: Placebos
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)