Study to Evaluate the Extended Overall Survival (OS) Data From PARSIFAL Study (The PARSIFAL-LONG Study)

NCT06525675 | Completed FDA Drug

• 1 other identifier: MEDOPP507
• Study Type: observational
• Target: 419
• Locations: 6 countries
• Sites: 36

Brief Summary

The goal of this study is to evaluate the extended Overall Survival (OS) from PARSIFAL trial - NCT02491983 focused on the efficacy and safety of palbociclib in combination with fulvestrant or letrozole in patients with Human Epidermal growth factor Receptor 2 (HER2)-negative, Endocrine Receptor (ER)-positive metastatic breast cancer. It was designed to test the superiority of fulvestrant plus palbociclib compared with letrozole plus palbociclib first and then the non-inferiority of fulvestrant plus palbociclib compared with letrozole plus palbociclib if the superiority objective was not achieved.

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer; Luminal Breast Cancer; HER2-negative Breast Cancer; ER-positive Breast Cancer

Keywords

breast cancer; metastatic breast cancer; luminal breast cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall Survival (OS) is defined as the time from randomization until death from any cause in the palbociclib plus fulvestrant group versus the palbociclib plus letrozole group

  24 months

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  24 months

• Overall Survival (OS)

  24 months

• Progression Free Survival (PFS)

  24 months

• Number of patients with the same subsequent antineoplastic therapy

  24 months

Study Arms (2)

Fulvestrant plus palbociclib (interventional arm)

Postmenopausal women and premenopausal women receiving Luteinizing Hormone-Releasing Hormone (LHRH) analogues, aged ≥ 18 years with ER positive and HER2 negative locally advanced or metastatic breast cancer that had not received any therapy for the metastatic disease. Patients are not eligible if they are candidates for a local treatment with a radical intention. Subjects must have histologic confirmation of the estrogen and/or progesterone-positive and HER2 negative receptors breast cancer. Evidence of measurable or evaluable metastatic disease is required.

Drug: Fulvestrant Injectable Product; Drug: Palbociclib 125mg

Letrozole plus palbociclib (control arm)

Postmenopausal women and premenopausal women receiving Luteinizing Hormone-Releasing Hormone (LHRH) analogues, aged ≥ 18 years with ER positive and HER2 negative locally advanced or metastatic breast cancer that had not received any therapy for the metastatic disease. Patients are not eligible if they are candidates for a local treatment with a radical intention. Subjects must have histologic confirmation of the estrogen and/or progesterone-positive and HER2 negative receptors breast cancer. Evidence of measurable or evaluable metastatic disease is required.

Drug: Letrozole 2.5mg; Drug: Palbociclib 125mg

Interventions

Fulvestrant Injectable Product DRUG

500 mg fulvestrant on days 1, 14, 28, and once monthly thereafter, administered intramuscularly.

Also known as: Faslodex®

Fulvestrant plus palbociclib (interventional arm)

Letrozole 2.5mg DRUG

2.5 mg letrozole per day, administered orally (continuous treatment)

Also known as: Letrozole

Letrozole plus palbociclib (control arm)

Palbociclib 125mg DRUG

orally administration 125 mg palbociclib per day (in cycles of 3 weeks of treatment followed by 1 week off)

Also known as: PD-0332991

Fulvestrant plus palbociclib (interventional arm); Letrozole plus palbociclib (control arm)

Eligibility Criteria

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

Study Population

Eligible women were aged 18 y or older with menopausal status and HER2-negative/ER-positive, unresectable, locally advanced, or metastatic breast cancer not treatable with curative intent. Patients had not received systemic therapy for advanced disease and had measurable or non measurable disease as defined by RECIST version 1.1. Endocrine therapy in the neoadjuvant or adjuvant setting was permitted if the patient had a disease-free interval of more than 12m from the completion of endocrine therapy. An Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 and adequate organ function were also required. Key exclusion criteria were visceral crisis and prior treatment with a CDK4/6 inhibitor.

You may qualify if:

• Patients previously randomized in the PARSIFAL trial (N = 486).
• Patients did not withdraw consent to participate in the PARSIFAL clinical trial.
• Postmenopausal women, as defined by any of the following criteria:
• Age 60 or over
• Age 45 to 59 years and meets ≥1 of the following criteria: amenorrhea for ≥ 24 months or amenorrhea for \< 24 months and follicle-stimulating hormone within the postmenopausal range (including patients with hysterectomy, prior hormone replacement therapy or chemotherapy-induced amenorrhea).
• Over 18 years of age and bilateral oophorectomy
• OR:
• Premenopausal women provided they are being treated with LHRH analogues for at least 28 days prior to study entry.
• Eastern Cooperative Oncology Group (ECOG) score lower or equal to 2.
• Histologically confirmed recurrent ER-positive (oestrogen and/or progesterone) HER2-negative locally advanced or metastatic BC patients (Breast cancer that have at least 1% of cells staging positive for ER should be considered ER-positive according to National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) guidelines.
• Patients should not be candidates for a local treatment with a radical intention.
• No prior hormonal or chemotherapy line in the metastatic setting.
• Patient must have measurable (according to RECIST 1.1) or non-measurable disease with these exceptions:
• Patients with only blastic bone lesions are not eligible.
• Patients with only pleural, peritoneal, or cardiac effusion, or meningeal carcinomatosis are not eligible.

You may not qualify if:

• Patients were excluded from the PARSIFAL trial if they met any of the following criteria:
• ER or HER2 unknown disease.
• HER2-positive disease based on local laboratory results (performed by immunohistochemistry/FISH)
• Locally advanced breast cancer candidate for a radical treatment.
• Prior endocrine therapy in the metastatic setting. (Neo)/Adjuvant endocrine therapy is allowed only if the disease-free interval between the end of endocrine therapy and the appearance of metastases in higher than 12 months.
• Patients with rapidly progressive visceral disease or visceral crisis.
• Have had a major surgery (defined as requiring general anesthesia) or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the study.
• Patients with an active, bleeding diathesis.
• Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or anti-coagulation treatment (The use of low molecular weight heparin is allowed as long as it is used as prophylaxis).
• Are unable to swallow tablets.
• History of malabsorption syndrome or other condition that would interfere with enteral absorption.
• Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent (excluding inhaled steroids).
• Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral oedema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
• Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any palbociclib excipients.
• Corrected QT Interval (QTc) \>480 msec on basal assessments, personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).

Sponsors & Collaborators

• MedSIR: lead
• Pfizer: collaborator

Study Sites (36)

Onkologická klinika Fakultní nemocnice Olomouc

Olomouc, Czechia

Location

General University Hospital in Prague

Prague, Czechia

Location

Hopital Tenon

Paris, France

Location

Hospital Europeo Georges Pompidou AP-HP

Paris, France

Location

Institut Curie

Paris, France

Location

Centre Paul Strauss

Strasbourg, 67000, France

Location

Institut Universitaire du Cancer Toulouse, Toulouse

Toulouse, France

Location

Klinikum Dessau (MVZ) - Frauenheilkunde

Dessau, Germany

Location

Istituti Ospitalieri Cremona

Cremona, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

Milan, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Ospedale San Gerardo

Monza, Italy

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital San Joan de Reus

Reus, Tarragona, Spain

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Hospital Universitary Vall D´Hebron

Barcelona, 08035, Spain

Location

Institut Català d' Oncologia L'Hospitalet (ICO)

Barcelona, Spain

Location

Institut Oncologic Baselga-Hospital Quiron Salud Barcelona

Barcelona, Spain

Location

Hospital Universitario de Basurto

Bilbao, 48013, Spain

Location

Hospital Provincial de Castellón

Castellon, Spain

Location

Hospital San Pedro Alcántara

Cáceres, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 28091, Spain

Location

ICO Girona

Girona, Spain

Location

Hospital Universitario Juan Ramón Jiménez

Huelva, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

CHUS Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Fundación Instituto Valenciano de Oncología (IVO)

Valencia, 46009, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, United Kingdom

Location

Barts Cancer Institute

London, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Abertawe Bro Morgannwg University Local Health Board, Singleton Hospital

Swansea, SA127BR, United Kingdom

Location

Royal Cornwall Hospital NHS Trust

Truro, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; Letrozole; palbociclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Antonio Llombart

  Arnau de Vilanova Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: July 29, 2024
• Study Start: July 18, 2022
• Primary Completion: May 26, 2024
• Study Completion: September 2, 2024
• Last Updated: December 13, 2024

Record last verified: 2024-07

Locations

IT (4); GB (5); DE (1); ES (19); FR (5); CZ (2)