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

NCT03238196 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VICC BRE 16126
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 6

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.

Conditions

Metastatic Breast Cancer

Keywords

FGFR inhibitor; ER+ metastatic breast cancer; CDK4/6 inhibitor; Endocrine therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

  Number of participants with DLT in the first cycle for the determination of the MTD.

  From the time of randomization up to 4 weeks of treatment (cycle 1), for each patient

Secondary Outcomes (8)

• Progression-free Survival

  Imaging studies will be performed every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

• Overall Response Rate

  Imaging studies will be performed every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

• Clinical Benefit Rate (CBR; Complete Response + Partial Response + Stable Disease Without Disease Progression at 6 Months)

  From the time of randomization up to 6 months for each patient

• Pharmacokinetic Assessment of Erdafitinib - Area Under the Curve (AUC)

  From the time of randomization up to 4 weeks of treatment for each patient

• Pharmacokinetic Assessment of Erdafitinib - Cmax (Maximum Plasma Concentration)

  From the time of randomization up to 4 weeks of treatment for each patient

Other Outcomes (4)

• Serial Measurements of Serum Phosphate, Calcium, Vitamin D, Parathyroid Hormone (PTH), FGF23, sFGFR2, sFGFR3, and sFGFR4

  During the first 8 weeks of treatment (days 1, 8, 15, 22 of cycle 1 and days 1 and 15 of cycle 2)

• FGFR1 Amplification Levels by FISH and cfDNA

  At study entry (baseline)

• Next Generation Sequencing

  At study entry (baseline)

Study Arms (2)

Escalation

EXPERIMENTAL

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

Drug: Erdafitinib; Drug: Palbociclib; Drug: Fulvestrant

Expansion

EXPERIMENTAL

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

Drug: Erdafitinib; Drug: Palbociclib; Drug: Fulvestrant

Interventions

Erdafitinib DRUG

4mg - 8mg

Also known as: JNJ-42756493

Escalation; Expansion

Palbociclib DRUG

125 mg

Also known as: Ibrance

Escalation; Expansion

Fulvestrant DRUG

500 mg

Also known as: Faslodex

Escalation; Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify 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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baptist Memorial Hospital MEMPHIS

Memphis, Tennessee, 38120, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

Location

Related Publications (1)

• 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.

  PMID: 40627530 DERIVED

Related Links

• Clinical Trials Webpage - Vanderbilt-Ingram Cancer Center
• Mycancergenome - FGFR1 Webpage

MeSH Terms

Conditions

Breast Neoplasms

Interventions

erdafitinib; palbociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Brent Rexer, MD, PhD, Assistant Professor
• Organization: Vanderbilt-Ingram Cancer Center

brent.rexer@vumc.org

615-322-4967

Study Officials

• Brent Rexer, MD, PhD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: August 3, 2017
• Study Start: August 18, 2017
• Primary Completion: April 30, 2021
• Study Completion: March 20, 2024
• Last Updated: November 14, 2024
• Results First Posted: February 16, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)