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Fulvestrant, Palbociclib, and Erdafitinib in Treating Patients with Estrogen Receptor Positive, HER2 Negative, and FGFR Amplified Stage IV Breast Cancer That Is Recurrent or Cannot Be Removed by Surgery

Trial Status: Active

This phase Ib trial studies the side effects and best dose of erdafitinib when given together with fulvestrant and palbociclib in treating patients with estrogen receptor positive, HER2 negative, and FGFR amplified stage IV breast cancer that has come back or cannot be removed by surgery. Drugs used in chemotherapy, such as fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Palbociclib and erdafitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fulvestrant, palbociclib, and erdafitinib may work better in treating patients with breast cancer.

Inclusion Criteria

  • Patients (female or male) must provide informed written consent and must complete all screening assessments as outlined in the protocol
  • Patients must be able to swallow and retain oral medication
  • Female patients of no childbearing potential must be post-menopausal; post-menopausal female subjects should be defined prior to protocol enrollment by any of the following: * Subjects at least 60 years of age; OR * Subjects under 60 years of age and naturally (spontaneous, no alternative pathologic or physiological cause) amenorrhea for at least 12 months; OR * Medical ovarian failure confirmed by follicle-stimulating hormone (FSH) and estradiol levels in the post menopausal range per local institutional normal range; OR * Prior bilateral oophorectomy; OR * Prior radiation castration with amenorrhea for at least 6 months; OR * Treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (such as goserelin acetate or leuprolide acetate) is permitted for induction of ovarian suppression as long as it has been initiated at least 28 days prior to study enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
  • Clinical stage IV or inoperable locoregional recurrent invasive mammary carcinoma that is: * ER+ and/or progesterone receptor (PgR)+ (>= 1% positive stained cells) by immunohistochemistry (IHC) * HER2-negative (by IHC or fluorescence in situ hybridization [FISH], per American Society of Clinical Oncology [ASCO] guidelines) * FGFR1-4 amplified (may be determined by local assessment through either targeted capture next generation sequencing [NGS], plasma cell-free tumor [cf] DNA or FISH [in the case of FGFR1 amplifications]* in 50% of the patients participating in the expansion cohort of the trial [not necessary in the escalation cohort]) ** Cases will be considered as FGFR1-positive (‘amplified’) under one of the following conditions: *** The FGFR1/CEN8 ratio is >= 2.0 *** The average number of FGFR1 signals per tumor cell nucleus is >= 6 * Evaluable (may have either measurable or non-measurable disease)
  • Patients must have available tissue (archived formalin-fixed paraffin embedded [FFPE] blocks or fresh frozen biopsy from primary tumor or metastatic tumor biopsy) for correlative studies; tissue source needs to be located and available at the time of registration (tissue needs to be submitted within 3 weeks of study initiation); patients will not be able to start study drugs without tissue availability
  • Patients must have had at least one line of therapy in the metastatic setting
  • Current use of any of the drugs listed on the Cautionary Concomitant Med list has to be approved by the study chair
  • Absolute neutrophil count (ANC) >= 1,500/mm^3 (obtained within 2 weeks from study drug initiation)
  • Platelet count >= 100,000/mm^3 (obtained within 2 weeks from study drug initiation)
  • Hemoglobin (HgB) >= 9.0 g/dL (obtained within 2 weeks from study drug initiation)
  • Creatinine clearance >= 40 mL/min/1.73 m^2 (obtained within 2 weeks from study drug initiation)
  • Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) if no liver metastasis present; SGOT, SGPT =< 4 x ULN if liver metastasis present (obtained within 2 weeks from study drug initiation)
  • Albumin >= 2.0 g/dL (obtained within 2 weeks from study drug initiation)
  • Total serum bilirubin =< 1.5 x ULN (=< 3 x ULN or direct bilirubin =< 1.5 x ULN if known Gilbert’s syndrome) (obtained within 2 weeks from study drug initiation)
  • Potassium within institutional normal limits (obtained within 2 weeks from study drug initiation)
  • Phosphorus =< institutional upper limit of normal (obtained within 2 weeks from study drug initiation)

Exclusion Criteria

  • Prior use of an FGFR inhibitor
  • More than 2 lines of chemotherapy in the metastatic setting; no limit on endocrine therapy lines; prior exposure to CDK4/6 inhibitor acceptable
  • Radiation therapy =< 2 weeks prior to study entry; patients who have received prior radiotherapy must have recovered from toxicity (=< grade 1) induced by this treatment (except for alopecia)
  • Prior cancer therapy (except for endocrine therapy) must have been discontinued for 1 week prior to initiation of study drugs
  • Concurrent anti-cancer therapy other than the ones specified in the protocol is not permitted during study participation; bisphosphonates or denosumab are allowed
  • Major surgery within 4 weeks of enrollment
  • Herbal preparations are not allowed throughout the study, and should be discontinued 14 days prior to initiation of study treatment
  • Any corneal or retinal abnormality likely to increase the risk of eye toxicity, such as: * Current corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration * Uncontrolled glaucoma despite standard of care therapy * Diabetic retinopathy with macular edema * Known active wet, age-related macular degeneration (AMD) * Known central serous retinopathy (CSR) or retinal vascular occlusion (RVO)
  • Uncontrolled intercurrent illness including, but not limited to: * Malabsorption syndrome significantly affecting gastrointestinal function * Ongoing or active infection requiring antibiotics/antivirals * Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy) * Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease) * Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months * Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, version 4.03, grade 3]) * Fridericia's correction formula (QTcF) >= 480 msec on screening electrocardiography (EKG) * Known history of clinically significant QT/corrected QT (QTc) prolongation or torsades de pointes (TdP) * ST depression or elevation of >= 1.5 mm in 2 or more leads * Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2 that does not resolve within a few days when adequately treated with anti-diarrhea medications * Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary * Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment and be off steroids) * Known history of chronic liver or chronic renal failure * Poor wound healing capacity


University of Alabama at Birmingham Cancer Center
Contact: Andres Forero-Torres


San Francisco
UCSF Medical Center-Mount Zion
Contact: Hope S. Rugo

New York

New York
Memorial Sloan Kettering Cancer Center
Contact: Komal Jhaveri


University of Pittsburgh Cancer Institute (UPCI)
Contact: Rachel C. Jankowitz


Vanderbilt University / Ingram Cancer Center
Status: ACTIVE
Contact: Ingrid Alina Mayer
Phone: 615-936-2033


UT Southwestern / Simmons Cancer Center-Dallas
Contact: Barbara Jean B. Haley
Phone: 214-648-4180


I. To determine the safety and tolerability of fulvestrant, palbociclib and erdafitinib in patients with estrogen receptor (ER)+/HER2-/FGFR-amplified metastatic breast cancer (MBC).


I. To determine the anti-tumor effect of fulvestrant, palbociclib and erdafitinib in patients with ER+/HER2-/FGFR-amplified MBC.

II. Pharmacokinetic assessments of erdafitinib.


I. To determine pharmacodynamic biomarkers of FGFR inhibition.

II. To determine the therapeutic predictive role of FGFR1-4, CCND1-2, CDK4 and CDK6 amplifications, and RB1 and ESR1 mutations on clinical outcome.

III. To determine if the FGFR1 amplification levels by fluorescence in situ hybridization (FISH) and cell-free deoxyribonucleic acid (cfDNA) is an early surrogate of response.

IV. To determine if the cfDNA results at disease progression show new genomic alterations potentially associated with resistance to CDK4/6 and FGFR inhibition.

OUTLINE: This is a dose-escalation study of erdafitinib.

Patients receive fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and on day 1 of subsequent cycles, palbociclib orally (PO) once daily (QD) on days 1-21, and erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Vanderbilt University / Ingram Cancer Center

Principal Investigator
Ingrid Alina Mayer

  • Primary ID VICCBRE16126
  • Secondary IDs NCI-2017-01346
  • ID NCT03238196