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

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, multi-institution, phase Ib trial that evaluates the safety and tolerability and preliminary anti-tumor activity of fulvestrant, palbociclib and erdafitinib in patients with ER+/HER2-/FGFR-amplified metastatic breast cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: Genentech, Inc.; National Cancer Institute (NCI)
• Treatments: Estradiol; Fulvestrant; Palbociclib

Criteria

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