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

NCT ID: NCT03809988

Last Updated: 2023-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-05
• Study Completion Date: 2022-11-30

Brief Summary

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

Detailed Description

Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC that had previously received first-line endocrine therapy in combination with palbociclib and had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not eligible if they are candidates for a local treatment with a curative intention. Evidence of either measurable and biopsiable metastatic disease (as for Response Evaluation Criteria In Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required. Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone (LHRH) analogues.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional Arm (Arm A)

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).

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

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

Endocrine therapy

Intervention Type: DRUG

Endocrine therapy alone (letrozole or fulvestrant)

Control Arm (Arm B)

Patients will receive endocrine therapy (letrozole or fulvestrant).

Group Type: ACTIVE_COMPARATOR

Endocrine therapy

Intervention Type: DRUG

Endocrine therapy alone (letrozole or fulvestrant)

Interventions

Palbociclib

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

Intervention Type: DRUG

Endocrine therapy

Endocrine therapy alone (letrozole or fulvestrant)

Intervention Type: DRUG

Other Intervention Names

IBRANCE; letrozole; fulvestrant

Eligibility Criteria

Inclusion Criteria

1. Female patients over 18 years of age.

2. 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:

1. Age ≥60 years;

2. 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;

3. Documented bilateral oophorectomy.

3. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.

4. Life expectancy greater or equal to 12 weeks.

5. Histologically proven diagnosed of ABC not amenable to curative treatment.

6. 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.

7. 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.

8. 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).

9. 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.

10. 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.

11. Patients should not have been treated in the advanced setting with at least one of these endocrine therapy options: either fulvestrant or AI.

12. Patients must have measurable disease or evaluable disease according to RECIST criteria v.1.1. Patients with only bone lesions are eligible.

13. Willingness and ability to provide tumor biopsy (if feasible) both at the time of the inclusion and after disease progression in order to perform exploratory studies. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee.

14. Patients agree to collection of blood samples (liquid biopsy) at the time of inclusion, after 2 weeks of treatment, and upon progression or study termination.

15. Adequate organ function: (Hematological, hepatic and renal)

16. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

17. Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent form prior to participation in any study-related activities.

18. Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1

Exclusion Criteria

1. HR or HER2 unknown disease.

2. HER2-positive disease based on local laboratory results (performed by IHC / ISH test).

3. Locally ABC candidate for curative treatment.

4. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or symptomatic progressive visceral disease.

5. Prior therapy with any other CDK4/6 inhibitor different from palbociclib.

6. 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.

7. Patients are currently receiving food or drugs known to be strong inducers or inhibitors of CYP3A4.

8. 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.

9. 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.

10. 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.

11. 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.

12. Use of concurrent investigational agents or other concomitant anticancer therapies.

13. 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).

14. Serious concomitant systemic disorder (e.g., active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator).

15. Unable to swallow capsules or tablets.

16. History of malabsorption syndrome or other condition that would interfere with enteral absorption.

17. Any of the following within 6 months of randomization:

myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI-CTCAE v.5.0 grade ≥2, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.

18. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade ≥ 2.

19. Known hypersensitivity to palbociclib or any of its excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

MedSIR

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José Perez

Role: PRINCIPAL_INVESTIGATOR

MedSIR

Locations

Hôpital Jean Minjoz

Besançon, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

Centre Georges François Leclerc

Dijon, , France

CHD Vendee

La Roche-sur-Yon, , France

Hopital Europeen Georges Pompidou

Paris, , France

Hôpital Tenon AP-HP

Paris, , France

Centre Paul Strauss

Strasbourg, , France

University Hospital Dresden-GYN

Dresden, , Germany

Kliniken Essen Mitte

Essen, , Germany

Universitätsklinikum Essen Frauenklinik

Essen, , Germany

AGAPLESION Markus Krankenhaus

Frankfurt, , Germany

Technical University Munich

Munich, , Germany

UKM Brustzentrum

Münster, , Germany

Klinikum Ernst von Bergmann

Potsdam, , Germany

Klinikum Mutterhaus der Borromäerinnen Trier

Trier, , Germany

Ospedale Civili Brescia

Brescia, , Italy

Instituto Europeo di Oncologia

Milan, , Italy

Oncologia Medica Ospedale di Prato

Prato, , Italy

Policlinico Universitario Campus Bio-medico

Roma, , Italy

Onkološki Inštitut Ljubljana

Ljubljana, , Slovenia

Univerzitetni klinicni center Maribor Oddelek za onkologijo

Maribor, , Slovenia

ICO Badalona

Badalona, Barcelona, Spain

Hospital Provincial de Castellón

Castelló, Castelló, Spain

Consorci Sanitari de Terrassa

Terrassa, Terrasa, Spain

Centro Oncológico de Galicia

A Coruña, , Spain

Institut Català d'Oncologia Bellvitge

Barcelona, , Spain

H. Vall Hebrón

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital de Basurto

Bilbao, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Institut Català d'Oncologia

Girona, , Spain

Hospital Arnau de Vilanova

Lleida, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario Sanchinarro

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitari Son Espases

Palma de Mallorca, , Spain

Hospital Sant Joan

Reus, , Spain

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Instituto Valenciano de Oncología IVO

Valencia, , Spain

Hospital General Universitari de Valencia

Valencia, , Spain

Hospital Arnau de Vilanova de Valencia

Valencia, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Hospital Álvaro Cunqueiro

Vigo, , Spain

Hospital Lozano Blesa

Zaragoza, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

Darent Valley Hospital by Dartford and Gravesham NHS Trust

Dartford, , United Kingdom

Beatson West of Scotland Cancer Center

Glasgow, , United Kingdom

Barts Cancer Institute

London, , United Kingdom

Kent Oncology Department

Maidstone, , United Kingdom

Abertawe Bro Morgannwg University Local Health Board, Singleton Hospital

Swansea, , United Kingdom

Royal Cornwall Hospital NHS Trust

Truro, , United Kingdom

Countries

France; Germany; Italy; Slovenia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40294349 (View on PubMed)

Other Identifiers

2017-002781-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MedOPP068

Identifier Type: -

Identifier Source: org_study_id