Clinical trial · Interventional
Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY
NCT01942135CI-TRIAL-00075747completedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Breast Cancer | Malignant Breast Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Fulvestrant | Drug | Fulvestrant | ALIAS |
| Palbociclib | Drug | Palbociclib | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A
- description
- Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
- interventionNames
- Drug: Palbociclib
- Drug: Fulvestrant
- type
- ACTIVE_COMPARATOR
- label
- Arm B
- description
- Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
- interventionNames
- Drug: Placebo
- Drug: Fulvestrant
Primary outcomes (1)
- measure
- Progression-Free Survival (PFS) as Assessed by the Investigator
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy * Confirmed diagnosis of HR+/HER2- breast cancer * Any menopausal status * Progressed within 12 months from prior adjuvant or progressed within 1 month from prior advanced/metastatic endocrine breast cancer therapy * On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization. * Measurable disease defined by RECIST version 1.1, or bone-only disease * Eastern Cooperative Oncology Group (ECOG) PS 0-1 * Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures * Patient must agree to provide tumor tissue from metastatic tissue at baseline Exclusion Criteria: * Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway * Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases * Major surgery or any anti-cancer therapy within 2 weeks of randomization * Prior stem cell or bone marrow transplantation * Use of potent CYP3A4 inhibitors or inducers
References
Publications (23)
- DERIVEDLi H, Wu Y, Zou H, Koner S, Plichta JK, Tolaney SM, Zhang J, He YW, Wei Q, Tang L, Zhang H, Zhang B, Guo Y, Chen X, Li K, Lian L, Ma F, Luo S. Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials. EBioMedicine. 2024 Jul;105:105186. doi: 10.1016/j.ebiom.2024.105186. Epub 2024 Jun 10. PMID 38861871
- DERIVEDRugo HS, Im SA, Joy AA, Shparyk Y, Walshe JM, Sleckman B, Loi S, Theall KP, Kim S, Huang X, Bananis E, Mahtani R, Finn RS, Dieras V. Effect of palbociclib plus endocrine therapy on time to chemotherapy across subgroups of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Post hoc analyses from PALOMA-2 and PALOMA-3. Breast. 2022 Dec;66:324-331. doi: 10.1016/j.breast.2022.11.005. Epub 2022 Nov 15. PMID 36463643
- DERIVEDZhu Z, Turner NC, Loi S, Andre F, Martin M, Dieras V, Gelmon KA, Harbeck N, Zhang C, Cao JQ, Yan Z, Lu DR, Wei P, VanArsdale TL, Rejto PA, Huang X, Rugo HS, Loibl S, Cristofanilli M, Finn RS, Liu Y. Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib. NPJ Precis Oncol. 2022 Aug 16;6(1):56. doi: 10.1038/s41698-022-00297-1. PMID 35974168
- DERIVEDRugo HS, Cristofanilli M, Loibl S, Harbeck N, DeMichele A, Iwata H, Park YH, Brufsky A, Theall KP, Huang X, McRoy L, Bananis E, Turner NC. Prognostic Factors for Overall Survival in Patients with Hormone Receptor-Positive Advanced Breast Cancer: Analyses From PALOMA-3. Oncologist. 2021 Aug;26(8):e1339-e1346. doi: 10.1002/onco.13833. Epub 2021 Jun 12. PMID 34037282
- DERIVEDIwata H, Umeyama Y, Liu Y, Zhang Z, Schnell P, Mori Y, Fletcher O, Marshall JC, Johnson JG, Wood LS, Toi M, Finn RS, Turner NC, Bartlett CH, Cristofanilli M. Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3. Oncologist. 2021 Jul;26(7):e1143-e1155. doi: 10.1002/onco.13811. Epub 2021 Jun 7. PMID 33955129