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Clinical Trials Search at Vanderbilt-Ingram Cancer Center

Fulvestrant, Palbociclib, and pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Treating Patients with Estrogen Receptor Positive, HER2 Negative, and FGFR Amplified Stage IV Breast Cancer That Is Recurrent or Cannot Be Removed by Surgery

This phase Ib trial studies the side effects and best dose of pan-FGFR tyrosine kinase inhibitor JNJ-42756493 when given together with fulvestrant and palbociclib in treating patients with estrogen receptor positive, HER2 negative, and FGFR amplified stage IV breast cancer that has come back or cannot be removed by surgery. Drugs used in chemotherapy, such as fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Palbociclib and pan-FGFR tyrosine kinase inhibitor JNJ-42756493 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fulvestrant, palbociclib, and pan-FGFR tyrosine kinase inhibitor JNJ-42756493 may work better in treating patients with breast cancer.
Breast
Phase I
Adults
Hormonal Therapy, Mol. targeted/Immunotherapy/Biologics
Erdafitinib, Fulvestrant, Palbociclib
Mayer, Ingrid
Local
BAPT-Baptist Hospital (MEMPHIS), Memorial Sloan-Kettering Cancer Center, UT Southwestern Medical Center, University of Alabama/Birmingham, University of California, San Francisco, University of Pittsburgh, Vanderbilt University
08-10-2017
Treatment
VICCBRE16126
NCT03238196

Eligibility

18 Years
BOTH
NO
Inclusion Criteria:

Patients (female or male) must provide informed written consent and must complete all screening assessments as outlined in the protocol

Patients must be able to swallow and retain oral medication

Female patients of no childbearing potential must be post-menopausal; post-menopausal female subjects should be defined prior to protocol enrollment by any of the following: * Subjects at least 60 years of age; OR * Subjects 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

Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1

Clinical stage IV or inoperable locoregional recurrent invasive mammary carcinoma that is: * ER+ and/or progesterone receptor (PgR)+ (>= 1% positive stained cells) by immunohistochemistry (IHC) * HER2-negative (by IHC or fluorescence in situ hybridization [FISH], per American Society of Clinical Oncology [ASCO] guidelines) * FGFR1-4 amplified (may be determined by local assessment through either targeted capture next generation sequencing [NGS], plasma cell-free tumor [cf] DNA or FISH [in the case of FGFR1 amplifications]* in 50% of the patients participating in the expansion cohort of the trial [not necessary in the escalation cohort]) ** Cases will be considered as FGFR1-positive (‘amplified’) under one of the following conditions: *** The FGFR1/CEN8 ratio is >= 2.0 *** The average number of FGFR1 signals per tumor cell nucleus is >= 6 * Evaluable (may have either measurable or non-measurable disease)

Patients must have available tissue (archived formalin-fixed paraffin embedded [FFPE] blocks or fresh frozen biopsy from primary tumor or metastatic tumor biopsy) for correlative studies; tissue source needs to be located and available at the time of registration (tissue needs to be submitted within 3 weeks of study initiation); patients will not be able to start study drugs without tissue availability

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

Absolute neutrophil count (ANC) >= 1,500/mm^3 (obtained within 2 weeks from study drug initiation)

Platelet count >= 100,000/mm^3 (obtained within 2 weeks from study drug initiation)

Hemoglobin (HgB) >= 9.0 g/dL (obtained within 2 weeks from study drug initiation)

Creatinine clearance >= 40 mL/min/1.73 m^2 (obtained within 2 weeks from study drug initiation)

Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =
Albumin >= 2.0 g/dL (obtained within 2 weeks from study drug initiation)

Total serum bilirubin =
Potassium within institutional normal limits (obtained within 2 weeks from study drug initiation)

Phosphorus =


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 =
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 (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy) * Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease) * 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]) * Fridericia's correction formula (QTcF) >= 480 msec on screening electrocardiography (EKG) * Known history of clinically significant QT/corrected 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 >= Common Terminology Criteria for Adverse Events (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

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