Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer

Inclusion Criteria:

Patients must be able to swallow and retain oral medication
Patients must be ≥ 18 years of age
Female patients of no childbearing potential must be post-menopausal. Postmenopausal female subjects should be defined prior to protocol enrollment by any of the following:
Participants at least 60 years of age; OR
Participants 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
Patients must have ECOG performance status 0 - 1
Patients must have clinical stage IV or inoperable locoregional recurrent invasive mammary carcinoma that is:
ER+ and/or PgR+ (≥ 1% positive stained cells) by immunohistochemistry (IHC)
HER2-negative (by IHC or FISH, per ASCO guidelines)
FGFR1 - 4 amplified
Patients must have evaluable (may have either measurable or non-measurable) disease
Patients must have available tissue for FGFR determination
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
Patients must have adequate hematologic, hepatic and renal function. All laboratory tests must be obtained within 2 weeks from study drug initiation. These include:
ANC ≥ 1,500/mm3
Platelet count ≥ 100,000/mm3
HgB ≥ 9.0 g/dL
Creatinine clearance ≥ 40 mL/min/1.73 m2
SGOT, SGPT ≤ 2.5 x ULN if no liver metastasis present; SGOT, SGPT ≤ 4 x ULN if liver metastasis present
Albumin ≥ 2.0 g/dL
Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN if known Gilbert's syndrome)
Potassium within institutional normal limits
Phosphorus ≤ institutional upper limit of normal

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 (COPD > grade 2, lung conditions requiring oxygen therapy)
Symptomatic congestive heart failure
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]
QTcF ≥ 480 msec on screening EKG
Known history of clinically significant 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 ≥ 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