Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Palbociclib

Goserelin

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

Enzyme Inhibitors

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

All patients in all arms will receive Fulvestrant 500mg

Fulvestrant 500mg

Palbociclib 125mg

Goserelin 3.6 MG

Placebos

Jean-Marc Nabholtz, MD

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

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.

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

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®

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

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

radiological response according to the WHO criteria (US/Mammography/MRI)

Rate of breast conservative surgery will be assessed and compared between two arms

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

Evaluation and comparison of Disease Free Survival (DFS) and Overall Survival (OS) between two arms

AstraZeneca

Pfizer

Genomic Health®, Inc.

International Cancer Research Group, United Arab Emirates

Patients who initiate ET in first line of advanced disease, they could be patients de novo with no previous ET or patients who received adjuvant ET and experience disease recurrence more than one year after its completion.

Patients will be divided in two subgroups according to having or not received previous ET.

Patients in progression who are starting a first or second line of ET for advanced Breast Cancer (BC) and showing one of following the hormone-resistance criteria to any ET:

For first line:

* Primary hormone-resistance: disease recurrence occurs within the first two years of adjuvant ET.
* Secondary hormone-resistance: disease recurrence occurs after the first two years of adjuvant ET or during the first year after its completion.

For second line:

* Primary hormone-resistance: disease progression occurs within the first 6 months of ET for advanced disease.
* Secondary hormone-resistance: disease progression occurs after the first 6 months of ET for advanced disease.

Patients will be divided in two subgroups according to having primary or secondary hormone-resistance.

Study Director

This is a multicentre, prospective, observational, no post-authorization study. This study will be opened for recruitment approximately for 12 months for a pilot phase including at least 25-30 patients and 6 controls and for 12 additional months to complete patient and control inclusion until 90 patients and 20 control depending on the first part study results.

After enrolment, patients will be assigned to one of the following cohorts according to their level of hormone-resistance:

* Cohort A (hormone-sensitive disease).
* Cohort B (hormone-resistant disease).

In both cohorts it will be collected residual pre-treatment tumor samples from metastatic lesions, preferably obtained after last treatment just prior to study entry, and/or primary breast tumor; as well as serial blood samples at baseline, after 6 weeks, at the same time of radiological re-evaluation (3 months after ET initiation) and at progressive disease (PD) which will be used for serial analytic determinations of the expression profiles of Natural Killer (NK) cells, other lymphoid innate cells, NKG2D ligands, cytokines and other possible biomarkers; in addition to obtain local data of hemogram and estradiol, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels.

Patients who have participated in the study during their first line of ET are eligible to participate after progression, when they initiate the second line of ET (in this case, inclusion/exclusion criteria should be checked newly and Informed Consent Form (ICF) signed again).

From the control population it will be collected blood and local data (e.g. hemogram, estradiol, FSH and LH levels), in a single time-point after ICF signature.

Plasma, Peripheral Blood Mononuclear Cells and tumor tissue.

Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer

The NIKOLE Study: Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer

Amount of the different populations of innate immune cells (e.g. NK cells, ILC1, ILC2 and ILC3) detected in tumor tissue and/or serial peripheral blood samples.

Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment).

Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form.

It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry.

Activation level of the different populations of innate immune cells (e.g. NK cells, ILC1, ILC2 and ILC3) detected in tumor tissue and/or serial peripheral blood samples.

Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment).

Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form.

It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry.

Analyses of the expression level of cytokines and/or rNKG2D ligands in tumor tissue and/or serial peripheral blood samples.

Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment).

Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form.

It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry.

Progression Free Survival (PFS) defined as the time from the start of therapy to the first documented progressive disease, or death from any cause, whichever occurs first. Progressive disease will be based on the investigator's assessment according to the standard institutional guidelines, and following as much as possible RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month).

OR rate (ORR) is defined as the Complete Response (CR) + Partial Response (PR) out of the patients who had measurable disease at baseline, according to the standard institutional guidelines and following as much as possible the RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month).

Clinical Benefit (CB): is defined as complete response (CR), partial response (PR), or stable disease (SD) lasting more than 24 weeks; based on the investigator's assessment according to the standard institutional guidelines, and following as much as possible according to the RECIST version 1.1. The definition of Response/non-Response and Stable Disease will be based on the RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month).

Spanish Breast Cancer Research Group

Menopause

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Docetaxel

Letrozole

Epirubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Aromatase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel

Drugs: letrozole + palbociclib combination

Fluorouracile

Paul Cottu, MD

Suzette Delaloge, MD

The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. In line with the most recent recommendations on targeted anticancer therapies, the investigators have designed a parallel phase II randomized trial with early stopping rules 26, which will able in the meantime to build a unique prospective collection of tumor tissue, pre- and post-treatment.

Efficacy of Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women

Open-label, Randomized, Multicenter, International, Parallel Exploratory Phase II Study, Comparing 3 FEC-3 Docetaxel Chemotherapy to Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula.

The toxicity will be evaluated according to the scale CTC-AE version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fulvestrant Versus Fulvestrant Plus Palbociclib in Operable Breast Cancer Responding to Fulvestrant	NCT03447132	Breast Neoplasm...	Fulvestrant 500... Palbociclib 125... Goserelin 3.6 M... Placebos	18 Years -	International Cancer Research Group, United Arab Emirates
Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer	NCT04370522	Metastatic Brea...		18 Years -	Spanish Breast Cancer Research Group
Efficacy of Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women	NCT02400567	Neoadjuvant Ope...	Fluorouracile Epirubicin Cyclophosphamid... Letrozole Palbociclib	18 Years -	UNICANCER
Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer	NCT04370522	Metastatic Brea...		18 Years -	Spanish Breast Cancer Research Group

Spots Global Cancer Trial Database for luminal

Every month we try and update this database with for luminal cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for luminal

Every month we try and update this database with for luminal cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for luminal cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.