Clinical trial NCT02491983: Palbociclib in Combination With Fulvestrant or Letrozole in Patients With ER+, HER2- Advanced Breast Cancer
Official title: A Randomized, Multicenter, Open-label, Phase II Trial to Evaluate the Efficacy and Safety of Palbociclib in Combination With Fulvestrant or Letrozole in Patients With HER2 Negative, ER+ Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: metastatic breast cancer
Endocrine receptors positive
HER-2 negative
Lead sponsor: MedSIR
Sponsor class: OTHER
First posted: 2015-07-08
Enrollment: 486
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an international, randomized, open-label, controlled, multicenter phase II clinical trial to investigate and compare the safety and efficacy of palbociclib combined with fulvestrant or letrozole in women with ER+, HER2- locally advanced or metastatic breast cancer.

Detailed description: Patients will be stratified by site of disease (visceral vs. non-visceral) and by onset of metastatic disease diagnose (patients metastatic de novo versus non de novo).

Eligibility criteria: Inclusion Criteria:

1. Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy
2. Confirmed diagnosis of HR+/HER2- breast cancer
3. Post-menopausal status
4. No prior chemotherapy line in the metastatic setting
5. Measurable disease defined by RECIST version 1.1, or non-measurable disease
6. Eastern Cooperative Oncology Group (ECOG) PS 0-1
7. Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures
8. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCICTCAE version 4.0 Grade equal or minor than 1

Exclusion Criteria:

1. ER or HER2 unknown disease
2. HER2 positive disease based on local laboratory results
3. Locally advanced breast cancer candidate for a radical treatment
4. Prior (neo)adjuvant endocrine treatment with DFI ≤ 12-months from completion of treatment.
5. Patients with rapidly progressive visceral disease or visceral crisis.
6. Major surgery within 4 weeks of start of study drug
7. Patients with an active, bleeding diathesis
8. Serious concomitant systemic disorder incompatible with the study
9. Are unable to swallow tablets
10. Chronic daily treatment with corticosteroids with a dose of ≥ 10mg/day methylprednisolone equivalent
11. Known active uncontrolled or symptomatic CNS metastases
12. Known hypersensitivity to letrozole, fulvestrant or any of their excipients, or to any PD-0332991 excipients
13. 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
14. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug

Primary outcomes:
measure: 1-year Progression Free Survival
timeFrame: One year
Secondary outcomes:
measure: Number of Participants With Grade 3/4 Adverse Events, SAEs, Deaths and Discontinuations •
timeFrame: Through study completion. From baseline up to 51 months.
measure: Time To Progression (TTP)
timeFrame: Through study completion. From baseline up to 51 months.
measure: Overall Survival (OS)
timeFrame: Through study completion. From baseline up to 51 months.
measure: Clinical Benefit Rate
timeFrame: Through study completion. From baseline up to 51 months.
measure: Overall Response Rate
timeFrame: Through study completion. From baseline up to 51 months.
Other outcomes:
Locations:
city: Olomouc
country: Czechia
facility: MedSIR investigative site
city: Prague
country: Czechia
facility: MedSIR investigative site
city: Prague
country: Czechia
facility: MedSIR investigative site
city: Paris
country: France
facility: MedSIR investigative site
city: Paris
country: France
facility: MedSIR investigative site
city: Paris
country: France
facility: MedSIR investigative site
city: Strasbourg
country: France
facility: MedSIR investigative site
city: Toulouse
country: France
facility: MedSIR investigative site
city: Dessau
country: Germany
facility: MedSIR investigative site
city: Heidelberg
country: Germany
facility: MedSIR investigative site
city: Brindisi
country: Italy
facility: MedSIR investigative site
city: Cagliari
country: Italy
facility: MedSIR investigative site
city: Cremona
country: Italy
facility: MedSIR investigative site
city: Milan
country: Italy
facility: MedSIR investigative site
city: Milan
country: Italy
facility: MedSIR investigative site
city: Modena
country: Italy
facility: MedSIR investigative site
city: Monza
country: Italy
facility: MedSIR investigative site
city: Piacenza
country: Italy
facility: MedSIR investigative site
city: Torino
country: Italy
facility: MedSIR investigative site
city: Moscow
country: Russian Federation
facility: MedSIR investigative site
city: Moscow
country: Russian Federation
facility: MedSIR investigative site
city: Saint Petersburg
country: Russian Federation
facility: MedSIR investigative site
city: Yaroslavl
country: Russian Federation
facility: MedSIR investigative site
city: Barcelona
country: Spain
facility: MedSIR investigative site
city: Barcelona
country: Spain
facility: MedSIR investigative site
city: Barcelona
country: Spain
facility: MedSIR investigative site
city: Bilbao
country: Spain
facility: MedSIR investigative site
city: Castelló
country: Spain
facility: MedSIR investigative site
city: Cordoba
country: Spain
facility: MedSIR investigative site
city: Cáceres
country: Spain
facility: MedSIR investigative site
city: Girona
country: Spain
facility: MedSIR investigative site
city: Huelva
country: Spain
facility: MedSIR investigative site
city: Madrid
country: Spain
facility: MedSIR investigative site
city: Oviedo
country: Spain
facility: MedSIR investigative site
city: Pamplona
country: Spain
facility: MedSIR investigative site
city: Santiago de Compostela
country: Spain
facility: MedSIR investigative site
city: Sevilla
country: Spain
facility: MedSIR investigative site
city: Tarragona
country: Spain
facility: MedSIR investigative site
city: Valencia
country: Spain
facility: MedSIR investigative site
city: Zaragoza
country: Spain
facility: MedSIR investigative site B
city: Zaragoza
country: Spain
facility: MedSIR investigative site
city: Bath
country: United Kingdom
facility: MedSIR investigative site
city: London
country: United Kingdom
facility: MedSIR investigative site
city: Manchester
country: United Kingdom
facility: MedSIR investigative site
city: Nottingham
country: United Kingdom
facility: MedSIR investigative site
city: Romford
country: United Kingdom
facility: MedSIR investigative site
city: Swansea
country: United Kingdom
facility: MedSIR investigative site
city: Truro
country: United Kingdom
facility: MedSIR investigative site
Study officials:
affiliation: MedSIR
name: Antonio Llombart, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Cosimo S, Perez-Garcia JM, Bellet M, Dalenc F, Gil Gil MJ, Ruiz Borrego M, Gavila J, Sampayo-Cordero M, Aguirre E, Schmid P, Marme F, Gligorov J, Schneeweiss A, Albanell J, Zamora P, Wheatley D, Martinez-De Duenas E, Caranana V, Amillano K, Mina L, Malfettone A, Cortes J, Llombart-Cussac A. Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial. Oncologist. 2023 Jan 18;28(1):23-32. doi: 10.1093/oncolo/oyac205.
citation: Llombart-Cussac A, Perez-Garcia JM, Bellet M, Dalenc F, Gil-Gil M, Ruiz-Borrego M, Gavila J, Sampayo-Cordero M, Aguirre E, Schmid P, Marme F, Di Cosimo S, Gligorov J, Schneeweiss A, Albanell J, Zamora P, Wheatley D, Martinez-de Duenas E, Amillano K, Malfettone A, Cortes J; PARSIFAL Steering Committee and Trial Investigators. Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor-Positive, ERBB2-Negative Advanced Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021 Dec 1;7(12):1791-1799. doi: 10.1001/jamaoncol.2021.4301.