This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. To estimate the objective radiographic response rate to single agent rogaratinib (BAY 1163877) in two cohorts of patients with sarcoma: Cohort A defined as patients with a sarcoma which harbors an alteration in fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 identified by next-generation sequencing profiling, and Cohort B defined as patients with advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST). SECONDARY OBJECTIVES: I. To estimate progression-free survival (PFS) in patients in Cohort A and Cohort B treated with rogaratinib (BAY 1163877). II. Further assessment for safety and tolerability. EXPLORATORY OBJECTIVES: I. To evaluate serial measurements of FGFR and FGFR ligand in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing (RNA-seq) (pre-treatment biopsy and post-progression biopsy \[if available\]). II. Whole exome sequencing (WES) of the pre-treatment biopsy and post-progression biopsy (if available) to help identify mechanisms of resistance. III. To bank tumor material, germline deoxyribonucleic acid (DNA), and peripheral blood for potential future research for participating subjects who provide additional consent. IV. To explore rogaratinib exposure with pharmacodynamics effects (i.e., clinical response, toxicity, and markers of FGFR pathway inhibition). OUTLINE: Patients receive rogaratinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT throughout the study. Patients may also undergo blood sample collection on study. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Undergo biopsy
Undergo blood sample collection
Undergo CT scan and PET/CT scan
Undergo MRI
Undergo PET/CT scan
Given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Northwestern University
Chicago, Illinois, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
...and 8 more locations
Objective radiographic response
The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time frame: Up to 30 days after removal from study
Progression-free survival
Will be estimated using Kaplan-Meier method.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days after removal from study
Incidence of adverse events
Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Up to 30 days after removal from study
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.