Neoadjuvant Letrozole and Palbociclib in Patients With Stage II-IIIB Breast Cancer, HR+, HER2 -

NCT03819010 | Completed Phase 2

• 2 other identifiers: MedOPP1992018-001702-28
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 18

Brief Summary

This is an international, multicenter, open-label, non-comparative, Simon´s two-stage design, phase II clinical trial.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Difference on Recurrence Score between pre and post-treatment (molecular results)

  To explore after 6 months of treatment the ability of palbociclib in combination with letro-zole to induce global molecular changes measured by either the Oncotype DX Breast Recurrence Score® (the "Assay") test result at surgery (post-treatment Recurrence Score® (RS) result), or pathological Complete Response (pCR) in patients with aggres-sive luminal tumors (pre-treatment RS result 18-25 or 26-100, and Ki67\>20).

  6 months

Secondary Outcomes (7)

• Molecular changes

  6 months

• Molecular induction

  6 months of treatment

• Global molecular reduction

  6 months of treatment

• increase RS result

  6 months of treatment

• Evaluate the concordance rate between the RCB score (0- I vs. II-III) and the post-treatment RS result in both cohorts of patients after treatment with palbociclib in com-bination with letrozole;

  6 months of treatment

Other Outcomes (6)

• overall repsonse

  6 month of treatment

• duration of response

  6 month of treatment

• Time to response

  6 month of treatment

Study Arms (2)

Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib

ACTIVE COMPARATOR

Letrozole (2,5 mg/day during 28 days of each Cycle) + Palbociclib (125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer interventions: Letrozol (2,5 mg/day during 28 days of each Cycle)+ Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer

Drug: Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib

Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib

ACTIVE COMPARATOR

Letrozole (2,5 mg/day during 28 days of each Cycle) + Palbociclib (125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer interventions: Letrozol (2,5 mg/day during 28 days of each Cycle)+ Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer

Drug: Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib

Interventions

Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib DRUG

Letrozole(2,5 mg/day during 28 days of each Cycle) + Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer for patients with pre-treatment recurrence Score of 18-25

Also known as: None othe intervention name

Pre treatment Recurrence Score:18-25 Letrozole + Palbociclib

Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib DRUG

Letrozole(2,5 mg/day during 28 days of each Cycle) + Palbociclib(125mg/day during 21 days of each cycle of 28 days) as neoadjuvant treatment during 6 cycles before surgery of Breast Cancer for patients with pre-treatment recurrence Score of 26-100

Also known as: None othe intervention name

Pre treatment Recurrence Score:26-100 Letrozole + Palbociclib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pre and post menopausal females
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients over 18 years of age.
• Patients have been informed about the nature of study, have agreed to participate in the study, and have signed the informed consent form prior to participation in any study-related activities.
• Premenopausal and postmenopausal women. Premenopausal women must be treated with LHRH analogue since patient pre- registration. Premenopausal or postmenopausal status should have been established before starting study treatment with letrozole plus palbociclib based on the following classification:
• Postmenopausal status is defined as either:
• Prior bilateral oophorectomy; Or
• Age\>60 years; Or
• Age\<60 years and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression, and follicle-stimulating hormone (FSH) and estradiol in postmenopausal range.
• Premenopausal status is defined as all those women who do not meet any of above criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Histologically confirmed infiltrating breast cancer.
• HR-positive (estrogen receptor \[ER\]-positive and/or progesterone receptor \[PgR\]-positive) EBCs (breast cancers that have at least 10% of cells staging positive for ER and/or PgR). ER and/or PgR status will be centrally confirmed by using immunohistochemistry (IHC) testing for an Allred score of 6-8 in at least one of them.
• Patients with HER2-negative breast cancer through in situ hybridization test (fluorescence in situ hybridization \[FISH\], chromogenic in situ hybridization \[CISH\], or silver enhanced in situ hybridization \[SISH\]) or negative immunohistochemical status of 0, 1+, or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required.
• Ki67 levels ≥ 20% confirmed by IHC testing in a central laboratory.
• Tumor size \> 2,0 cm (T2-4 according to TNM staging system, but always \> 2,0 cm) by mammogram, breast ultrasound, or breast magnetic resonance imaging (MRI).
• Patients must have a measurable disease by mammogram and/or breast ultrasound.

You may not qualify if:

• Patients will be excluded from the study if they meet ANY of the following criteria:
• Metastatic progression (M1, according to TNM staging system).
• Substantial nodal involvement (N\>2, according to TNM staging system).
• Non-large tumor (T0-1, according to TNM staging system).
• Bilateral breast carcinoma.
• Inflammatory carcinoma (T4d, according to TNM staging system).
• Patient with multicentric or multifocal (more than 2 lesions) breast cancer.
• Excisional biopsy of the primary tumor.
• Known hypersensitivity to any palbociclib excipients.
• Known hypersensitivity to any letrozole excipients.
• Patients unable to swallow tablets.
• Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
• Previous radiotherapy on the ipsilateral chest wall for the treatment of any other malignancy.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within four weeks of start of study treatment, or patients who have not recovered from the side effects of any major surgery, or patients that may require major surgery during the course of the study.
• Have a serious concomitant systemic disorder (i.e., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).

Sponsors & Collaborators

• MedSIR: lead
• Pfizer: collaborator

Study Sites (18)

Hospital da Luz

Lisbon, Portugal

Location

Hospital Fernando Fonseca

Lisbon, Portugal

Location

Portuguese Institute of Oncology of Oporto

Porto, Portugal

Location

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

ICO l'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08007, Spain

Location

Hospital de Jaén

Jaén, Jaén, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, Spain

Location

H. Vall Hebrón

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Reina Sofia

Córdoba, Spain

Location

Onkologikoa

Donostia / San Sebastian, Spain

Location

Hospital Arnau de Vilanova

Lleida, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Antonio Llombart, PdH

  MedSIR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Two arms of patients (according to Recurrence Score results), but both arms will be treated with the same treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an international, multicenter, open-label, non-comparative, Simon´s two-stage design, phase II clinical trial.

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 28, 2019
• Study Start: May 7, 2019
• Primary Completion: July 30, 2019
• Study Completion: December 31, 2019
• Last Updated: November 27, 2020

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The trial separate 2 stage: Stage I it will be radomized 26 patients (20 Sites) from January 2019 to June2019 and Stage II: 40 patients (25 sites) from February 2020 to July 2020.
• Access Criteria: patient should be randomized od Data base of hospitals

Locations

ES (15); PT (3)