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 | Completed Phase 2 DMC

• 4 other identifiers: NeoPal - UC-0140/14042014-002560-33CARMINA04NEOPAL
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Neoadjuvant Operable Breast Cancer

Keywords

Luminal; Post menopausal; Breast conservation; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy

  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.

  21 weeks

Secondary Outcomes (4)

• Evaluation of the clinical response in each treatment arm as defined by clinical and ultrasound examination.

  21 weeks

• Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability

  21 weeks

• Correlation of the PAM50 risk of recurrence (ROR) score to its ability to predict RCB as defined in outcome 1

  21 weeks

• Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery.

  21 weeks

Study Arms (2)

Chemotherapy

ACTIVE COMPARATOR

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

Drug: Fluorouracile; Drug: Epirubicin; Drug: Cyclophosphamide

Letrozole Palbociclib

EXPERIMENTAL

Drugs: letrozole + palbociclib combination

Drug: Letrozole; Drug: Palbociclib

Interventions

Fluorouracile DRUG

Chemotherapy

Epirubicin DRUG

Chemotherapy

Cyclophosphamide DRUG

Chemotherapy

Letrozole DRUG

Letrozole Palbociclib

Palbociclib DRUG

Letrozole Palbociclib

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years, Post-menopausal women
• Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation - Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)
• Stage II-IIIA
• Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
• Non metastatic, M0
• ER-positive by IHC (Allred Score≥4)
• HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish
• Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation
• ECOG 0-1
• No prior systemic therapy for the present tumor
• Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:
• Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L
• Platelets ≥100,000/mm3 or ≥100 x 109/L
• Hemoglobin ≥9 g/dL
• Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤2.5 x upper limit of normal (ULN)

You may not qualify if:

• Non operable, bilateral, T4 or metastatic breast cancer
• Limited T2 breast cancer immediately accessible to conservative surgery
• Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
• Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
• Previous use of SERMs such as raloxifene
• Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 4 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures.
• Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
• History of any previous anti-cancer chemotherapy and any previous treatment using AI
• Concurrent administration of herbal preparations as complementary medicine.
• Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs, such as the inability to take oral medication in tablet form and malabsorption syndrome
• Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Sponsors & Collaborators

• UNICANCER: lead
• Pfizer: collaborator
• NanoString Technologies, Inc.: collaborator

Study Sites (2)

Institut Curie

Paris, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Cottu P, D'Hondt V, Dureau S, Lerebours F, Desmoulins I, Heudel PE, Duhoux FP, Levy C, Mouret-Reynier MA, Dalenc F, Frenel JS, Jouannaud C, Venat-Bouvet L, Nguyen S, Ferrero JM, Canon JL, Grenier J, Callens C, Gentien D, Lemonnier J, Vincent-Salomon A, Delaloge S. Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. Ann Oncol. 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448.

  PMID: 30307466 RESULT

Related Links

• Ann Oncol . 2018 Dec 1;29(12):2334-2340. doi: 10.1093/annonc/mdy448

MeSH Terms

Interventions

Fluorouracil; Epirubicin; Cyclophosphamide; Letrozole; palbociclib

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nitriles; Triazoles; Azoles

Study Officials

• Paul Cottu, MD

  Institut Curie Paris

  PRINCIPAL INVESTIGATOR

• Suzette Delaloge, MD

  Gustave roussy, Villejuif

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: March 27, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: September 1, 2020
• Last Updated: March 15, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (2)