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

NCT ID: NCT03238196

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-18
• Study Completion Date: 2024-03-20

Brief 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.

Detailed Description

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

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Escalation

Fulvestrant - injection into muscle 1 time per month

Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken)

Erdafitinib tablet taken by mouth 1 time per day

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: DRUG

4mg - 8mg

Palbociclib

Intervention Type: DRUG

125 mg

Fulvestrant

Intervention Type: DRUG

500 mg

Expansion

Fulvestrant - injection into muscle 1 time per month

Palbociclib capsule taken by mouth 1 time per day every 21 days followed by 1 week of rest (no drug taken)

Erdafitinib tablet taken by mouth 1 time per day

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: DRUG

4mg - 8mg

Palbociclib

Intervention Type: DRUG

125 mg

Fulvestrant

Intervention Type: DRUG

500 mg

Interventions

Erdafitinib

4mg - 8mg

Intervention Type: DRUG

Palbociclib

125 mg

Intervention Type: DRUG

Fulvestrant

500 mg

Intervention Type: DRUG

Other Intervention Names

JNJ-42756493; Ibrance; Faslodex

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Brent Rexer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brent Rexer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

University of Alabama

Birmingham, Alabama, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Baptist Memorial Hospital MEMPHIS

Memphis, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Countries

United States

References

Gonzalez-Ericsson PI, Unni N, Jhaveri K, Stringer-Reasor E, Liu Q, Wang Y, Sanchez V, Garcia G, Sanders ME, Lehmann BD, Balko JM, Park B, Rexer BN, Mayer IA, Arteaga CL. Phase Ib Trial of Fulvestrant, Palbociclib, and Erdafitinib, a pan-FGFR Tyrosine Kinase Inhibitor, in HR+/HER2- Metastatic Breast Cancer. Clin Cancer Res. 2025 Sep 2;31(17):3652-3661. doi: 10.1158/1078-0432.CCR-24-3803.

Reference Type: DERIVED

PMID: 40627530 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.vicc.org/ct/protocols.php?cancer-type=Breast

Clinical Trials Webpage - Vanderbilt-Ingram Cancer Center

https://www.mycancergenome.org/content/disease/breast-cancer/fgfr1/

Mycancergenome - FGFR1 Webpage

Other Identifiers

VICC BRE 16126

Identifier Type: -

Identifier Source: org_study_id