PAlbociclib and Circulating Tumor DNA for ESR1 Mutation Detection
PADA-1
Randomized, Open Label, Multicentric Phase III Trial to Evaluate the Safety and Efficacy of Palbociclib in Combination With HT Driven by ctDNA ESR1 Mutation Monitoring in ER+, HER2-negative Metastatic Breast Cancer Patients
2 other identifiers
interventional
1,017
1 country
82
Brief Summary
This study is a randomized, open-label, multicentric, phase III trial conducted in patients receiving aromatase inhibitor and palbociclib as first line therapy for estrogen receptor (ER)-positive HER2-negative metastatic breast cancer and which aims to evaluate, at the onset of ESR1 mutations in circulating tumor DNA, the efficacy of a change of the hormone therapy (aromatase inhibitor (AI) changed to fulvestrant) combined to palbociclib, together with the safety of hormone therapy and palbociclib combination in the overall population.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2017
Longer than P75 for phase_3
82 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 9, 2017
CompletedFirst Posted
Study publicly available on registry
March 14, 2017
CompletedStudy Start
First participant enrolled
March 22, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 22, 2025
CompletedNovember 18, 2025
October 1, 2025
4.1 years
February 9, 2017
November 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of treatment-emergent Adverse Events
Global safety of the combination of palbociclib + endocrine therapy in the whole population, with focus on hematological toxicities. Safety will be assessed by the collection of grade ≥3 adverse events, using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 - in all included patients.
Throughout study completion, up to 4 years
Progression-free survival (Step 2)
To assess whether a change of the hormone therapy associated with palbociclib will benefit patients for whom rising ESR1 mutations are detected during treatment with palbociclib and aromatase inhibitor. Progression-Free Survival (PFS) will be measured from the time of randomization to the time of tumor progression (as assessed by the investigator per RECIST v1.1) or death (whichever comes first) - in randomized patients.
From randomization to disease progression or death, up to 4 years
Secondary Outcomes (8)
Progression-free survival (step 3)
From cross-over, up to 4 years
Progression-free survival (step 1&2)
From inclusion, up to 4 years
Time to strategy failure from randomization (Step 2 and 3)
From randomization, up to 4 years
Chemotherapy-free survival (Step 2 and 3)
From randomization, up to 4 years
Incidence of treatment-emergent extra-hematological Adverse Events
Throughout study completion, up to 4 years
- +3 more secondary outcomes
Study Arms (3)
A- palbociclib + AI
EXPERIMENTALAfter randomization, the patient will be treated with palbociclib 125 mg once daily for 21 days followed by 7 days off to complete a 28-day cycle in combination with an aromatase inhibitor (letrozole, anastrozole or exemestane, according to physician's choice and according their respective summary product characteristics) administered once daily in a continuous scheme.
B- Palbociclib + fulvestrant
EXPERIMENTALAfter randomization, the patient will be treated with palbociclib 125 mg once daily for 21 days followed by 7 days off to complete a 28-day cycle in combination with fulvestrant, a selective estrogen receptor down-regulator, 500 mg administered intramuscularly on Days 1, 15, and 29 and once monthly thereafter.
Selection - Palbociclib + AI
EXPERIMENTALAll patients included into the study will be treated with palbociclib 125 mg once daily for 21 days followed by 7 days off to complete a 28-day cycle in combination with an aromatase inhibitor (letrozole, anastrozole or exemestane, according to physician's choice and according their respective summary product characteristics) administered once daily in a continuous scheme
Interventions
Palbociclib 125 mg once daily for 21 days followed by 7 days off to complete a 28-day cycle
Letrozole: 2.5 mg once daily on a continuous scheme (tablets, per os) Anastrozole:1 mg once daily on a continuous scheme (tablets , per os) Exemestane: 25 mg once daily on a continuous scheme (tablets, per os)
500 mg by intramuscular injection on days 1 and 15 of cycle one and then on day one of each subsequent cycle (28 days)
Eligibility Criteria
You may qualify if:
- Women with proven loco-regionally recurrent or metastatic adenocarcinoma of the breast not amenable to curative therapy with disease considered potentially sensitive to aromatase inhibitors Note: patients relapsing while on adjuvant tamoxifen or other non-aromatase inhibitor adjuvant endocrine therapy and patients relapsing more than one year after the end of aromatase inhibitor adjuvant therapy are eligible for the present study;
- Age ≥18 years;
- Life expectancy \>3 months;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2;
- Estrogen Receptor (ER)-positive and HER2-negative breast cancer. Where available, assessment of Estrogen Receptor status should be based on the most recent tumor sample; to be considered as ER-positive, the most recent breast cancer tissue examined must display at least 10% of cancer cells with positive ER staining;
- Tumor block (primary tumor or metastasis) available;
- No prior systemic anti-cancer therapy for metastatic or advanced disease (chemotherapy, targeted therapy or hormone therapy); prior initiation of LHRH agonist or bone-directed agents is however allowed);
- Menopausal patients or patients with suppressed ovarian function
- Women with bilateral oophorectomy
- Postmenopausal women, as defined by any of the following criteria:
- Age 60 or over;
- Age 50 to 59 years and meets one of the following criteria:
- Amenorrhea for ≥24 months and follicle-stimulating hormone within the postmenopausal range;
- patients with hysterectomy or chemotherapy-induced amenorrhea must display follicle-stimulating hormone within the postmenopausal range;
- Other women, provided they are being treated with monthly LHRH analogues (first injection performed ≥7 days before the treatment initiation) and are willing to continue to receive LHRH agonist therapy for the duration of the trial;
- +15 more criteria
You may not qualify if:
- Locally advanced breast cancer or loco-regional relapse amenable for any treatment with curative intent;
- Her2-positive or equivocal tumor status either on the primary or on the recurrent tumor, defined as IHC3+, Fish/Cish amplified or Fish/Cish equivocal according to the ASCO2015 criteria;
- Prior endocrine therapy in the metastatic setting is not allowed;
- Prior treatment with any CDK 4/6 inhibitor in the adjuvant or metastatic setting (neoadjuvant/preoperative treatment is allowed); however, prior therapy with another targeted treatment in the adjuvant setting is allowed;
- Visceral crisis: Advanced, symptomatic, visceral spread that is at risk of life-threatening complication in the short term and that requires chemotherapy;
- Any major surgery (defined as requiring general anaesthesia) or significant traumatic injury within 4 weeks of treatment initiation or patients that may require major surgery during the course of the study; however, surgical diagnostic procedure is allowed (even if performed under general anaesthesia);
- Known, active bleeding diathesis;
- Any serious known concomitant systemic disorder (e.g. known 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);
- Patients unable to swallow tablets;
- History of mal-absorption syndrome or other condition that would interfere with enteral absorption;
- Chronic daily treatment with corticosteroids with a dose of ≥10 mg/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 and off anticonvulsants and steroids for at least 4 weeks before treatment start;
- Known hypersensitivity to letrozole, anastrozole, exemestane, fulvestrant, palbociclib or any of their excipients;
- Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia);
- Patients treated within the last 7 days prior to treatment start in the trial with drug that are known to be CYP3A4 inhibitors, drugs that are known to be CIP3A4 inducers, who underwent a grapefruit cure;
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (82)
Centre Hospitalier Universitaire
Amiens, France
Clinique de l'Europe
Amiens, France
Institut de Cancérologie de l'Ouest - Site Paul Papin
Angers, France
Centre Hospitalier d'Auxerre
Auxerre, France
Institut Sainte Catherine
Avignon, France
Centre Hospitalier de Beauvais
Beauvais, France
Centre Hospitalier de Blois
Blois, France
Clinique Tivoli Ducos
Bordeaux, France
Institut Bergonié
Bordeaux, France
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France
Centre Hospitalier de boulogne sur Mer
Boulogne-sur-Mer, France
Centre Hospitalier Fleyriat
Bourg-en-Bresse, France
CHRU Morvan
Brest, France
Clinique PASTEUR-CFRO
Brest, France
Centre Francois Baclesse
Caen, France
Centre Hospitalier René Dubos
Cergy-Pontoise, France
Medipole de Savoie
Challes-les-Eaux, France
Centre Hôpital Sainte Marie
Chalon-sur-Saône, France
CH William Morey
Chalon-sur-Saône, France
Centre Hospitalier Métropole de Savoie
Chambéry, France
Centre Hospitalier de Cholet
Cholet, France
Centre Jean Perrin
Clermont-Ferrand, France
Pôle Santé République
Clermont-Ferrand, France
Centre Georges François Leclerc
Dijon, France
CHI Fréjus St-Raphaël
Fréjus, France
Institut Daniel Hollard - Groupe Hospitalier Mutualiste de Grenoble
Grenoble, France
Centre Hospitalier Départemental de Vendée
La Roche-sur-Yon, France
Clinique du Cap d'Or
La Seyne-sur-Mer, France
Centre Hospitalier de Versailles
Le Chesnay, France
Centre Hospitalier le Mans
Le Mans, France
Institut Hospitalier Franco-Britannique
Levallois-Perret, France
CHU Dupuytren
Limoges, France
Clinique François Chénieux
Limoges, France
Centre Hospitalier Bretagne Sud
Lorient, France
Centre Leon Berard
Lyon, France
Clinique de la Sauvegarde
Lyon, France
Hôpital privé Jean Mermoz
Lyon, France
Hôpital Européen Marseille
Marseille, France
Hôpital Saint Joseph
Marseille, France
Institut Paoli Calmettes
Marseille, France
Centre d'Oncologie radiothérapie de Macon
Mâcon, France
Clinique Claude Bernard
Metz, France
Centre Hospitalier ANNECY GENEVOIS
Metz-Tessy, France
CH Mont de Marsan
Mont-de-Marsan, France
Centre Hospitalier Montceau les mines
Montceau-les-Mines, France
ICM - Val d'Aurelle
Montpellier, France
Centre d'Oncologie de Gentilly
Nancy, France
Hopital Privé du Confluent
Nantes, France
Centre Antoine Lacassagne
Nice, France
Centre ONCOGARD - Institut de Cancérologie du Gard
Nîmes, France
Institut Curie
Paris, 75005, France
Hopital Diaconesses-Croix Saint Simon
Paris, France
Hopital Européen Georges Pompidou
Paris, France
Saint Louis Hospital
Paris, France
Centre Hospitalier de Pau
Pau, France
Centre Catalan d'Oncologie
Perpignan, France
Polyclinique Francheville
Périgueux, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
CARIO - Centre Armoricain Radiothérapie Imagerie Médicale et Oncologi
Plérin, France
Centre Hospitalier de Cornouaille
Quimper, France
Clinique de la Croix du Sud
Quint-Fonsegrives, France
Centre Eugène Marquis
Rennes, France
Centre de radiothérapie et d'oncologie médicale LE-CROME
Ris-Orangis, France
Centre Henri Becquerel
Rouen, France
Centre Hospitalier Saint-Brieuc
Saint-Brieuc, France
Institut Curie - Hôpital René Huguenin
Saint-Cloud, France
CHP Saint Grégoire
Saint-Grégoire, France
Institut de Cancérologie de l'Ouest - Site René Gauducheau
Saint-Herblain, France
Clinique Mutualiste de l'Estuaire
Saint-Nazaire, France
Institut de cancérologie lucien Neuwith
Saint-Priest-en-Jarez, France
Centre Hospitalier de Broussais
St-Malo, France
Centre Paul Stauss
Strasbourg, France
Clinique de l'Orangerie
Strasbourg, France
Clinique Sainte Anne
Strasbourg, France
Hôpitaux Universitaires de Strasbourg
Strasbourg, France
Hôpitaux du Léman
Thonon-les-Bains, France
Clinique Pasteur
Toulouse, France
Institut Claudius Regaud
Toulouse, France
Centre Hospitalier de Tours - Hopital Bretonneau
Tours, France
Centre Hospitalier Bretagne Atlantique
Vannes, France
UNEOS Site Hôpital Robert Schuman
Vantoux, France
Gustave Roussy
Villejuif, 94805, France
Related Publications (2)
Bidard FC, Hardy-Bessard AC, Dalenc F, Bachelot T, Pierga JY, de la Motte Rouge T, Sabatier R, Dubot C, Frenel JS, Ferrero JM, Ladoire S, Levy C, Mouret-Reynier MA, Lortholary A, Grenier J, Chakiba C, Stefani L, Plaza JE, Clatot F, Teixeira L, D'Hondt V, Vegas H, Derbel O, Garnier-Tixidre C, Canon JL, Pistilli B, Andre F, Arnould L, Pradines A, Bieche I, Callens C, Lemonnier J, Berger F, Delaloge S; PADA-1 investigators. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022 Nov;23(11):1367-1377. doi: 10.1016/S1470-2045(22)00555-1. Epub 2022 Sep 29.
PMID: 36183733DERIVEDBerger F, Marce M, Delaloge S, Hardy-Bessard AC, Bachelot T, Bieche I, Pradines A, De La Motte Rouge T, Canon JL, Andre F, Arnould L, Clatot F, Lemonnier J, Marques S, Bidard FC; PADA-1 investigators. Randomised, open-label, multicentric phase III trial to evaluate the safety and efficacy of palbociclib in combination with endocrine therapy, guided by ESR1 mutation monitoring in oestrogen receptor-positive, HER2-negative metastatic breast cancer patients: study design of PADA-1. BMJ Open. 2022 Mar 3;12(3):e055821. doi: 10.1136/bmjopen-2021-055821.
PMID: 35241469DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
François-Clément BIDARD, MD PhD
Institut Curie
- PRINCIPAL INVESTIGATOR
Suzette DELALOGE, MD PhD
Gustave Roussy, Cancer Campus, Grand Paris
- PRINCIPAL INVESTIGATOR
Anne-Claire HARDY BESSARD, MD
Centre Armoricain d'Oncologie
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 9, 2017
First Posted
March 14, 2017
Study Start
March 22, 2017
Primary Completion
April 30, 2021
Study Completion
September 22, 2025
Last Updated
November 18, 2025
Record last verified: 2025-10