Study of Infigratinib in Combination With Tamoxifen in Hormone Receptor Positive, HER2 Negative, FGFR Altered Advanced Breast Cancer

NCT04504331 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB-53650BRS0113K08CA252457NCI-2020-13784
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is identify the dose(s) of infigratinib to use in combination with tamoxifen to treat patients with a particular type of advanced breast cancer (hormone receptor-positive, HER2-negative, FGFR-altered breast cancer)

Conditions

Breast Cancer; HER2-negative Breast Cancer; ER Positive Breast Cancer; PR-Positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Dose-limiting Toxicities (DLTs)

  The primary outcome for this study is dose-limiting toxicities (DLTs) during the first 2 cycles of therapy. All grades per the Common Terminology Criteria for Adverse Events (CTCAE). DLT is defined as a related and clinically significant adverse event (AE), including missed doses due to a related AE.

  8 weeks

Secondary Outcomes (4)

• Number of Treatment Emergent Adverse Events (TEAE)

  From first dose to 30 days after the last dose of study drug (up to 94 days)

• Objective Tumor Response Rate

  From enrollment to day of scan (up to 64 days)

• Progression-free Survival (PFS)

  up to 9 months

• Clinical Benefit Rate

  6 months

Study Arms (3)

Cohort 1: Infigratinib (100mg) + Tamoxifen

EXPERIMENTAL

In study part 1 (dose exploration), participants will receive up to infigratinib 100 mg. 100 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen

Drug: Infigratinib; Drug: Tamoxifen; Drug: Omnipaque 350; Drug: Iopamidol; Diagnostic Test: Computed tomography (CT)

Cohort 2: Infigratinib (125mg) + Tamoxifen

EXPERIMENTAL

In study part 1 (dose exploration), participants will receive up to infigratinib 125 mg. 125 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen

Drug: Infigratinib; Drug: Tamoxifen; Drug: Omnipaque 350; Drug: Iopamidol; Diagnostic Test: Computed tomography (CT)

Cohort 3: Infigratinib (75mg) + Tamoxifen

EXPERIMENTAL

In study part 1 (dose exploration), participants will receive up to infigratinib 75 mg. 75 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen

Drug: Infigratinib; Drug: Tamoxifen; Drug: Omnipaque 350; Drug: Iopamidol; Diagnostic Test: Computed tomography (CT)

Interventions

Infigratinib DRUG

Oral dose

Also known as: FGFR 1-3-Selective Tyrosine Kinase Inhibitor, 872511-34-7, NVP-BGJ398, BGJ-398

Cohort 1: Infigratinib (100mg) + Tamoxifen; Cohort 2: Infigratinib (125mg) + Tamoxifen; Cohort 3: Infigratinib (75mg) + Tamoxifen

Tamoxifen DRUG

Oral Dose

Also known as: Nolvadex, Soltamox, Apo-Tamox, Tamofen, Tamone, ICI-46474

Cohort 1: Infigratinib (100mg) + Tamoxifen; Cohort 2: Infigratinib (125mg) + Tamoxifen; Cohort 3: Infigratinib (75mg) + Tamoxifen

Omnipaque 350 DRUG

IV contrast agent

Also known as: Iohexol, Hexopaque, Nycodenz, Exypaque, Compound 545

Cohort 1: Infigratinib (100mg) + Tamoxifen; Cohort 2: Infigratinib (125mg) + Tamoxifen; Cohort 3: Infigratinib (75mg) + Tamoxifen

Iopamidol DRUG

IV contrast agent

Also known as: Isovue 300, Isovue 370, Iopamiro, Iopamiron, Scanlux, Niopam, Jopamidol, Solutrast

Cohort 1: Infigratinib (100mg) + Tamoxifen; Cohort 2: Infigratinib (125mg) + Tamoxifen; Cohort 3: Infigratinib (75mg) + Tamoxifen

Computed tomography (CT) DIAGNOSTIC_TEST

Computed tomography (CT) to assess disease state using Iopamidol and/or Omnipaque 350.

Cohort 1: Infigratinib (100mg) + Tamoxifen; Cohort 2: Infigratinib (125mg) + Tamoxifen; Cohort 3: Infigratinib (75mg) + Tamoxifen

Eligibility Criteria

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

You may qualify if:

• History of biopsy proven ER positive and/or PR positive, HER2 negative breast cancer and radiographic evidence of metastatic disease, or locally recurrent unresectable disease. ER positivity and PR positivity are defined as ≥ 1% cells staining positive by immunohistochemistry. HER2 negativity is defined by immunohistochemistry (IHC) or Fluorescence in situ hybridization (FISH).
• Cancer subtype: Predicted integrative subtype classification of IC2 or IC6 according classifier on targeted sequencing data from FoundationOne.
• Evaluable or measurable disease, by cohort. Cohort 1 only: Evaluable or measurable disease, as defined by RECIST v1.1. Bone only disease is acceptable.
• Cohort 2 only: Measurable disease, as defined by RECIST v1.1.
• ≥ 18 years old
• Eastern Cooperative Oncology Group (ECOG) 0 to 2
• Prior cancer therapy (except for endocrine therapy, denosumab, or bisphosphonates) must be discontinued for 2 weeks prior to initiation of study drugs. Recovery from adverse events of previous cancer therapies to baseline or Grade 1 except for alopecia or stable Grade 2 neuropathy. Radiotherapy must also be completed at least 2 weeks prior to initiation of study drugs
• Absolute neutrophil count (ANC) ≥ 1,000/mm3
• Platelets ≥ 75,000/mm3
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.8 mg/dL (unless documented Gilbert's disease)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 90 U/L
• Estimated glomerular filtration rate (GFR) ≥ 45 mL/min
• Phosphorus between 2.5 and 4.5 mg/dL, inclusive
• Total corrected (for albumin) serum calcium between 8.5 and 10.5 mg/dL, inclusive

You may not qualify if:

• History of another primary malignancy within 3 years except adequately treated in situ carcinoma of the cervix or non melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study.
• Neurologic symptoms related to central nervous system metastases requiring increasing doses of corticosteroids. Note that subjects with central nervous system metastases are eligible if they are on a stable corticosteroid dose for at least 2 weeks preceding study entry.
• Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination. Subjects with asymptomatic ophthalmologic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
• Current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
• Current evidence of endocrine alterations of calcium/phosphate homeostasis, eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, or tumoral calcinosis.
• Currently receiving or planning during study participation to receive treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme inducing anti epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone. See Appendix B for a list of prohibited concomitant medications and supplements.
• Has consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or products containing juice of these fruits within 7 days prior to first dose of study drug.
• Have used amiodarone within 90 days prior to first dose of study drug.
• Has used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug. See Appendix B for a list of prohibited concomitant medications and supplements.
• Has used calcium or vitamin D within 3 days prior to first dose of study drug. Calcium supplementation may subsequently be used as clinically indicated (for hypocalcemia) on study.
• Have clinically significant cardiac disease including any of the following:
• Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2), left ventricular ejection fraction (LVEF) \< 50% or local lower limit of normal as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines \[Williams et al., 2018\])
• Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥ 2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality
• Unstable angina pectoris or acute myocardial infarction ≤ 3 months prior to first dose of study drug

Sponsors & Collaborators

• Jennifer Lee Caswell-Jin: lead
• National Cancer Institute (NCI): collaborator
• QED Therapeutics, a BridgeBio company: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

infigratinib; Tamoxifen; Iohexol; Iopamidol; Tomography, X-Ray Computed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Results Point of Contact

• Title: Jennifer Lee Caswell-Jin, MD
• Organization: Stanford Medicine at Stanford University

caswell@stanford.edu

1-310-332-6541

Study Officials

• Jennifer Lee Caswell-Jin

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Oncology)

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: October 13, 2020
• Primary Completion: October 22, 2021
• Study Completion: October 22, 2021
• Last Updated: February 12, 2026
• Results First Posted: June 1, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)