PALbociclib Rechallenge in horMone Receptor-posItive/HER2- Negative Advanced Breast Cancer (PALMIRA)

NCT03809988 | Completed Phase 2

• 2 other identifiers: MedOPP0682017-002781-48
• Study Type: interventional
• Target: 198
• Locations: 6 countries
• Sites: 53

Brief Summary

Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced breast cancer (ABC)

Conditions

Breast Cancer; Advanced Breast Cancer; Hormone Receptor Positive Tumor; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Keywords

HR; breast cancer; ABC; progesterone receptor; HER2; advanced; estrogen receptor

Outcome Measures

Primary Outcomes (1)

• PFS (Progression-free survival)

  From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) - defined as the period of time from randomization until objective tumor progression or death - assessed by RECIST criteria v.1.1, of continuation of palbociclib treatment combined with second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy in pre- and post- menopausal women with HR-positive/HER2-negative ABC.

  Baseline up to 29 months

Secondary Outcomes (7)

• Safety AEs

  Baseline up to 29 months

• Efficacy (ORR)

  Baseline up to 29 months

• Efficacy (Quality of Life)

  Baseline up to 42 months

• Efficacy of subgroup analysis

  Baseline up to 42 months

• Compare efficacy

  Baseline up to 42 months

Study Arms (2)

Interventional Arm (Arm A)

EXPERIMENTAL

Patients will receive palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks in combination with endocrine therapy (letrozole or fulvestrant).

Drug: Palbociclib; Drug: Endocrine therapy

Control Arm (Arm B)

ACTIVE COMPARATOR

Patients will receive endocrine therapy (letrozole or fulvestrant).

Drug: Endocrine therapy

Interventions

Palbociclib DRUG

Palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks

Also known as: IBRANCE

Interventional Arm (Arm A)

Endocrine therapy DRUG

Endocrine therapy alone (letrozole or fulvestrant)

Also known as: letrozole, fulvestrant

Control Arm (Arm B); Interventional Arm (Arm A)

Eligibility Criteria

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

You may qualify if:

• Female patients over 18 years of age.
• Pre-menopausal women provided they are being treated with a LHRH analogue for at least 28 days (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating hormone (FSH) must be confirmed analytically) prior to study entry or post- menopausal women as defined by any of the following criteria:
• Age ≥60 years;
• Age \<60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for postmenopausal females;
• Documented bilateral oophorectomy.
• Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.
• Life expectancy greater or equal to 12 weeks.
• Histologically proven diagnosed of ABC not amenable to curative treatment.
• Documented recurrent ER-positive and/or progesterone receptor (PgR)-positive (with ≥1% positive stained cells (according to NCCN National Comprehensive Cancer Network and ASCO American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by immunohistochemistry (IHC) or 2+ and negative by in situ hybridization (ISH) test) breast cancer in the advanced setting.
• Radiological or clinical evidence of disease progression on first- line combination of palbociclib plus endocrine therapy (aromatase inhibitor (AI) or fulvestrant). Patients previously treated with the combination of palbociclib and tamoxifen will be excluded.
• Patients have achieved clinical benefit criteria to a first-line palbociclib-based endocrine regimen (defined as at least stable disease ≥ 24 weeks or partial or complete response confirmed or unconfirmed).
• Patients must have been treated with a stable minimum dose of 75 mg palbociclib during the last 2 cycles of the prior palbociclib-based regimen.
• Last dose of palbociclib administered not later than 8 weeks and not earlier than 7 days from study entry, with the exception of patients relapsing on a palbociclib-based regimen in the adjuvant setting.
• Patients should not have been treated in the advanced setting with at least one of these endocrine therapy options: either fulvestrant or AI.
• Patients must have measurable disease or evaluable disease according to RECIST criteria v.1.1. Patients with only bone lesions are eligible.

You may not qualify if:

• HR or HER2 unknown disease.
• HER2-positive disease based on local laboratory results (performed by IHC / ISH test).
• Locally ABC candidate for curative treatment.
• Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or symptomatic progressive visceral disease.
• Prior therapy with any other CDK4/6 inhibitor different from palbociclib.
• Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
• Patients are currently receiving food or drugs known to be strong inducers or inhibitors of CYP3A4.
• Current or prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively- treated non-melanoma skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally eligible.
• No other systemic therapy for metastatic disease including chemotherapy, immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine therapy excluding first-line palbociclib-based regimen.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 2 weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients who may require major surgery during the study.
• Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
• Use of concurrent investigational agents or other concomitant anticancer therapies.
• Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon as it is used as prophylaxis intention).
• Serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).
• Unable to swallow capsules or tablets.

Sponsors & Collaborators

• MedSIR: lead
• Pfizer: collaborator

Study Sites (53)

Hôpital Jean Minjoz

Besançon, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHD Vendee

La Roche-sur-Yon, 85925, France

Location

Hopital Europeen Georges Pompidou

Paris, France

Location

Hôpital Tenon AP-HP

Paris, France

Location

Centre Paul Strauss

Strasbourg, 67000, France

Location

University Hospital Dresden-GYN

Dresden, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

Universitätsklinikum Essen Frauenklinik

Essen, Germany

Location

AGAPLESION Markus Krankenhaus

Frankfurt, Germany

Location

Technical University Munich

Munich, Germany

Location

UKM Brustzentrum

Münster, Germany

Location

Klinikum Ernst von Bergmann

Potsdam, Germany

Location

Klinikum Mutterhaus der Borromäerinnen Trier

Trier, Germany

Location

Ospedale Civili Brescia

Brescia, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Oncologia Medica Ospedale di Prato

Prato, Italy

Location

Policlinico Universitario Campus Bio-medico

Roma, Italy

Location

Onkološki Inštitut Ljubljana

Ljubljana, Slovenia

Location

Univerzitetni klinicni center Maribor Oddelek za onkologijo

Maribor, Slovenia

Location

ICO Badalona

Badalona, Barcelona, Spain

Location

Hospital Provincial de Castellón

Castelló, Castelló, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Terrasa, 08191, Spain

Location

Centro Oncológico de Galicia

A Coruña, 15009, Spain

Location

Institut Català d'Oncologia Bellvitge

Barcelona, 08908, Spain

Location

H. Vall Hebrón

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, 48013, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Institut Català d'Oncologia

Girona, Spain

Location

Hospital Arnau de Vilanova

Lleida, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Sanchinarro

Madrid, 28050, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, 07120, Spain

Location

Hospital Sant Joan

Reus, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Instituto Valenciano de Oncología IVO

Valencia, 46009, Spain

Location

Hospital General Universitari de Valencia

Valencia, 46014, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, 36312, Spain

Location

Hospital Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

Darent Valley Hospital by Dartford and Gravesham NHS Trust

Dartford, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, G12 0YN, United Kingdom

Location

Barts Cancer Institute

London, United Kingdom

Location

Kent Oncology Department

Maidstone, ME16 9QQ, United Kingdom

Location

Abertawe Bro Morgannwg University Local Health Board, Singleton Hospital

Swansea, SA127BR, United Kingdom

Location

Royal Cornwall Hospital NHS Trust

Truro, TR1 3LQ, United Kingdom

Location

Related Publications (1)

• Llombart-Cussac A, Harper-Wynne C, Perello A, Hennequin A, Fernandez-Ortega A, Colleoni M, Marin S, Quiroga V, Medioni J, Iranzo V, Wheatley D, Del Barco Berron S, Anton A, Dobi E, Ruiz-Borrego M, Alcala-Lopez D, Perez-Escuredo J, Antonarelli G, Sampayo-Cordero M, Perez-Garcia JM, Cortes J. Second-Line Endocrine Therapy With or Without Palbociclib Rechallenge in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: PALMIRA Trial. J Clin Oncol. 2025 Jun 20;43(18):2084-2093. doi: 10.1200/JCO-24-01865. Epub 2025 Apr 28.

  PMID: 40294349 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Letrozole; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• José Perez

  MedSIR

  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

Model Details: Randomized 2:1

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 18, 2019
• Study Start: April 5, 2019
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: September 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: During recruitment period
• Access Criteria: Oncology department

Locations

ES (26); GB (6); FR (7); DE (8); IT (4); SL (2)