Status:
COMPLETED
Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer
Lead Sponsor:
Vanderbilt-Ingram Cancer Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Metastatic Breast Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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+...
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-t...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
August 18 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 20 2024
Estimated Enrollment :
35 Patients enrolled
Trial Details
Trial ID
NCT03238196
Start Date
August 18 2017
End Date
March 20 2024
Last Update
November 14 2024
Active Locations (6)
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1
University of Alabama
Birmingham, Alabama, United States, 35233
2
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
3
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
4
Baptist Memorial Hospital MEMPHIS
Memphis, Tennessee, United States, 38120