NeoPAL: 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

Sponsor
UNICANCER (Other)
Overall Status
Completed
CT.gov ID
NCT02400567
Collaborator
Pfizer (Industry), NanoString Technologies, Inc. (Industry)
125
2
2
68
62.5
0.9

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
125 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 1, 2015
Actual Primary Completion Date :
Jan 1, 2018
Actual Study Completion Date :
Sep 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Chemotherapy

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

Drug: Fluorouracile

Drug: Epirubicin

Drug: Cyclophosphamide

Experimental: Letrozole Palbociclib

Drugs: letrozole + palbociclib combination

Drug: Letrozole

Drug: Palbociclib

Outcome Measures

Primary Outcome Measures

  1. Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy [21 weeks]

    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.

Secondary Outcome Measures

  1. Evaluation of the clinical response in each treatment arm as defined by clinical and ultrasound examination. [21 weeks]

  2. Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability [21 weeks]

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

  3. Correlation of the PAM50 risk of recurrence (ROR) score to its ability to predict RCB as defined in outcome 1 [21 weeks]

  4. Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery. [21 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Aged ≥ 18 years, Post-menopausal women

  2. 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)

  3. Stage II-IIIA

  4. Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)

  5. Non metastatic, M0

  6. ER-positive by IHC (Allred Score≥4)

  7. HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish

  8. Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation

  9. ECOG 0-1

  10. No prior systemic therapy for the present tumor

  11. 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)

  • Alkaline phosphatase ≤2.5 x ULN

  • Total serum bilirubin ≤1 x ULN

  • Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution

  1. Adequate cardiac functions, including:
  • 12 Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.

  • QTc interval ≤480 msec

  • No history of Torsades de Pointes or other symptomatic QTc abnormality.

  1. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures

  2. Signed informed consent and health insurance coverage

Exclusion Criteria:
  1. Non operable, bilateral, T4 or metastatic breast cancer

  2. Limited T2 breast cancer immediately accessible to conservative surgery

  3. 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

  4. Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment

  5. Previous use of SERMs such as raloxifene

  6. 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.

  7. 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

  8. History of any previous anti-cancer chemotherapy and any previous treatment using AI

  9. Concurrent administration of herbal preparations as complementary medicine.

  10. 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

  11. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institut Curie Paris France
2 Gustave Roussy Villejuif France

Sponsors and Collaborators

  • UNICANCER
  • Pfizer
  • NanoString Technologies, Inc.

Investigators

  • Principal Investigator: Paul Cottu, MD, Institut Curie Paris
  • Principal Investigator: Suzette Delaloge, MD, Gustave roussy, Villejuif

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
UNICANCER
ClinicalTrials.gov Identifier:
NCT02400567
Other Study ID Numbers:
  • NeoPal - UC-0140/1404
  • 2014-002560-33
  • CARMINA04
  • NEOPAL
First Posted:
Mar 27, 2015
Last Update Posted:
Mar 15, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by UNICANCER
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 15, 2022