Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy

NCT04130152 | Completed Early Phase 1

• 2 other identifiers: SOLTI-17102019-001275-36
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

Brief Summary

PROMETEO II is a single-arm window of opportunity trial to evaluate biologic and anti-proliferative effects of palbociclib and letrozole in HR+/HER2-negative operable breast cancer (BC) patients with residual disease after neoadjuvant chemotherapy (NAC) and help to identify biomarkers for better patient selection.

Conditions

Breast Cancer

Keywords

Palbociclib, residual disease, Neoadjuvant treatment, Ki67

Outcome Measures

Primary Outcomes (1)

• Complete Cell Cycle Arrest (CCCA)

  Complete Cell Cycle Arrest (CCCA) determined by Ki67\< 2.7% at surgery following treatment with palbociclib plus letrozole, by central laboratory

  Ki67 will be determined at surgery by central laboratory

Secondary Outcomes (4)

• Residual Cancer Burden (RCB)

  Pretreated sample before NAC, after NAC and at surgery 4 weeks after palbociclib and letrozole treatment

• Residual Cancer Burden (RCB)

  At surgery, 4 weeks after palbociclib and letrozole treatment

• Pathological complete response (pCR)

  At surgery, 4 weeks after palbociclib and letrozole treatment

• Incidence, duration and severity of Adverse Events (AEs)

  Up to 4 weeks

Other Outcomes (10)

• Change in gene expression of 752 genes

  Gene expression will be analyzed in pretreated sample and at surgery 4 weeks after palbociclib and letrozole treatment

• Changes of the PAM50 intrinsic subtypes

  Intrinsic subtype will be evaluated in pretreated sample, after NAC, and at surgery following therapy with palbociclib and letrozole.

• Rate of cell cycle suppression according to breast cancer subtype.

  At surgery, 4 weeks after palbociclib and letrozole treatment

Study Arms (1)

Palbociclib + Letrozole

EXPERIMENTAL

Palbociclib 125 mg once daily, day 1 to day 21, followed by 7 days off treatment in a 28-day cycle Letrozole: oral, 2.5 mg per day continuously. during the 28-day cycle. If the patient is pre-menopausal, ovarian suppression with luteinizing hormone-releasing hormone (LHRH) analogues (ie, triptorelin 3.75 mg intra-muscular (IM) or Goserelin 3,6 mg SC) must be initiated at least 2 weeks before palbociclib plus letrozole administration.

Drug: Palbociclib; Drug: Letrozole

Interventions

Palbociclib DRUG

Palbociclib 125 mg once daily, day 1 to day 21, followed by 7 days off treatment in a 28-day cycle

Also known as: Ibrance

Palbociclib + Letrozole

Letrozole DRUG

Letrozole: oral, 2.5 mg per day continuously. during the 28-day cycle.

Palbociclib + Letrozole

Eligibility Criteria

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

You may qualify if:

• Written and signed informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Female patients age ≥ 18 years.
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 to 1.
• Histologically confirmed non-metastatic primary HR-positive/HER2 negative breast cancer with all the following characteristics:
• Breast cancer eligible for surgery.
• ER-positive and/or PgR-positive and HER2-negative tumor by the most recent ASCO/CAP guidelines, before neoadjuvant treatment locally assessed.
• Ki67% ≥ 5% after neoadjuvant chemotherapy locally assessed (Dowsett M et al JNCI 2011).
• A lesion that could be confirmed by ultrasound (US) after neoadjuvant chemotherapy.
• Completed ≥80% total dose of an anthracycline/taxane-based neoadjuvant regimen planned. The allowed chemotherapy regimens will be AC (cyclophosphamide, doxorubicin) or EC (epirubicin, cyclophosphamide) 4 cycles followed by weekly paclitaxel x 12 or AC or EC 4 cycles followed by docetaxel 4 cycles. It would be acceptable to change the administration sequence to paclitaxel followed by AC/EC. AC can be given either a standard dose or in a dose-dense schedule. Paclitaxel could be administered as a solvent-based or Nanoparticle albumin-bound (Nab) formulation.
• Availability of a recent formalin-fixed paraffin-embedded (FFPE) tumor sample before NAC and a research tumor biopsy after NAC. Minimal sample requirements are to have at least 2 tumor cylinders with a minimal tissue surface of 10 mm2 tissue, containing at least 10% tumor cells and having enough tissue to do at least 2 cuts of 10 μm each.
• Adequate organ function determined within 28 days prior to enrollment, defined as follows:
• Hematological
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL (red blood cell transfusion and/or erythropoietin allowed)

You may not qualify if:

• Non-operable, locally advanced breast cancer (inoperable stage III) after NAC.
• Bilateral or metastatic invasive breast cancer at the time of the diagnosis.
• Known severe hypersensitivity reactions to compounds similar to palbociclib or to excipients or to endocrine treatments.
• History of any previous treatment using Aromatase inhibitors (AI) o selective estrogen receptor modulator (SERMs) in the past 5 years.
• Prior therapy with palbociclib or any cyclin-dependent kinase (CDK) inhibitor.
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to enrollment.
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization.
• Any surgery (not including minor procedures such as 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.
• Sentinel lymph node biopsy is not allowed before NAC.
• Diagnosis of any previous malignancy within the last 3 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
• Malabsorption syndrome or other condition that would interfere with enteric absorption.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
• Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomagnesemia).
• Any of the following within 6 months of enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
• Corrected QT interval (QTc) greater than 480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or know history of QTc prolongation, or Torsade de Pointes (TdP).

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Pfizer: collaborator

Study Sites (8)

Hospital General de Catalunya

Barcelona, Spain

Location

ICO Hospitalet

Barcelona, Spain

Location

Hospital 12 de octubre

Madrid, Spain

Location

Hospital Universitario Infanta Sofía

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

Complejo Hospitalario Santiago de Compostela (CHUS)

Santiago de Compostela, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Related Publications (1)

• Pernas S, Sanfeliu E, Villacampa G, Salvador J, Perello A, Gonzalez X, Jimenez B, Merino M, Palacios P, Pascual T, Alba E, Villanueva L, Chillara S, Ferrero-Cafiero JM, Galvan P, Prat A, Ciruelos E. Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy. NPJ Breast Cancer. 2024 Nov 26;10(1):101. doi: 10.1038/s41523-024-00710-x.

  PMID: 39592624 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm, Residual

Interventions

palbociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 17, 2019
• Study Start: November 21, 2019
• Primary Completion: January 26, 2022
• Study Completion: February 24, 2022
• Last Updated: October 25, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)