This pilot trial studies how rigsertib sodium works in treating patients with Recessive Dystrophic Epidermolysis bullosa (RDEB) with locally advanced Squamous Cell Carcinoma (SCC). Rigosertib may selectively target Epidermolysis bullosa (EB) cancer cells while leaving normal EB cells unaffected.
PRIMARY OBJECTIVES: I. To estimate the anti-tumor activity of oral or IV rigosertib in RDEB patients with advanced SCC that have failed prior standard of care, by determining the overall response rate (ORR) which is defined as the proportion of patients who achieve either a CR or a PR by RECIST v1.1 II. To evaluate the safety and tolerability of oral rigosertib administered either orally daily three weeks on, one week off or as 72h CIV infusions on day 1-3 of a two week-cycle for 8 cycles and then on day 1-3 of a 4 week cycle thereafter SECONDARY OBJECTIVES: I. Assess impact on quality of life (QoL) II. Biomarker analysis (to include markers of PI3K/Akt and PLK1 pathways) performed on all archival tissue from all patients EXPLORATORY OBJECTIVE: I. Exome sequencing of patient tumors before, during, and after treatment OUTLINE: Patients will receive rigosertib sodium as either oral capsules or IV infusion. Mode of application is determined by the responsible investigator depending on participant's needs, general condition, and possibility of ambulatory treatment or need of hospitalization. Patients will take oral rigosertib continuously for a total of three weeks of a four-week cycle (three weeks on, one week off drug). For IV treatment, patients will receive rigosertib IV administered as a 72-hr continuous infusion on Days 1, 2 and 3 of a 2-week cycle for the first eight 2-week cycles, then on Days 1, 2 and 3 of a 4-week cycle thereafter. Patients will receive treatment over a 52 week period. After completion of study treatment, patients are followed periodically every 3 months over a 12 month period.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
given PO or 72 hour continuous infusion
Ancillary studies
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Overall Response Rate (ORR)
Defined as the proportion of patients who achieve either a complete response (CR) or partial response (PR)
Time frame: baseline up to12 months post treatment
Incidence of treatment-related adverse events
Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. Results will be reported as an aggregate of the adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 terminology and grading.
Time frame: baseline up to12 months post treatment
Quality of Life Epidermolysis Bullosa (QOLEB) questionnaire
Descriptive methods used to analyze scores from QOLEB questionnaire. It consists of 17 questions with four response choices from "not at all" to "constant"
Time frame: baseline up to12 months post treatment
Biomarker Analysis
Fixed tissue will be assessed using immuno-histochemistry with antibodies raised against phosphorylated AKT (p473 Akt), phosphorylated C-RAF (p-S338 RAF), phosphorylated ERK and cleaved caspase.
Time frame: baseline up to12 months post treatment
Efficacy of rigosertib sodium treatment: The Objective Response Rate
The Objective Response Rate (ORR) will be computed with the corresponding exact binomial 90% confidence interval.
Time frame: baseline to end of treatment (52 weeks)
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