Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Hope Rugo

Description

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.

Official Title

A Phase Ib Trial of Fulvestrant, Palbociclib (CDK4/6 Inhibitor) and Erdafitinib (JNJ- 42756493,Pan-FGFR Tyrosine Kinase Inhibitor) in ER+/HER2-/FGFR-Amplified Metastatic Breast Cancer (MBC)

Details

Primary Objectives

• To determine the safety and tolerability of fulvestrant, palbociclib and erdafitinib in patients with ER+/HER2-/FGFR-amplified MBC.

Secondary Objectives

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

Correlative Objectives

  • To determine the therapeutic predictive role of FGFR1-4, CCND1-2, CDK4 and CDK6 amplifications, and RB1 and ESR1 mutations on clinical outcome
  • To determine if the FGFR1 amplification levels is an early surrogate of response
  • To determine if the cfDNA results at disease progression show new genomic alterations potentially associated with resistance to CDK4/6 and FGFR inhibition
  • To determine pharmacodynamic biomarkers of FGFR inhibition

Keywords

Metastatic Breast Cancer FGFR inhibitor ER+ metastatic breast cancer CDK4/6 inhibitor Endocrine therapy Breast Neoplasms Fulvestrant Palbociclib Estradiol Erdafitinib Escalation Expansion

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • University of California San Francicso not yet accepting patients
    San Francisco California 94158 United States
  • University of Texas Southwestern Simmons Comprehensive Cancer Center not yet accepting patients
    Dallas Texas 75235 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Vanderbilt-Ingram Cancer Center
Links
Clinical Trials Webpage - Vanderbilt-Ingram Cancer Center
Mycancergenome - FGFR1 Webpage
ID
NCT03238196
Phase
Phase 1
Lead Scientist
Hope Rugo
Study Type
Interventional
Last Updated