Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC
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|ClinicalTrials.gov Identifier: NCT04177498|
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : September 1, 2021
|Condition or disease||Intervention/treatment||Phase|
|Recessive Dystrophic Epidermolysis Bullosa||Drug: Rigosertib Sodium Other: Quality-of-Life Assessment||Early Phase 1|
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
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
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 (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot, Open Study to Assess Efficacy and Safety of Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated Locally Advanced/Metastatic Squamous Cell Carcinoma|
|Actual Study Start Date :||August 24, 2021|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||June 2023|
Experimental: Treatment (rigosertib sodium)
Patients receive rigosertib sodium either oral or IV over a 52 week period. Patients will take oral rigosertib continuously for a total of three weeks, every four-week cycle (three weeks on, one week off drug). For IV, rigosertib is 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.
Drug: Rigosertib Sodium
given PO or 72 hour continuous infusion
Other Name: ON 01910.Na
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Overall Response Rate (ORR) [ Time Frame: baseline up to12 months post treatment ]Defined as the proportion of patients who achieve either a complete response (CR) or partial response (PR)
- Incidence of treatment-related adverse events [ Time Frame: baseline up to12 months post treatment ]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.
- Quality of Life Epidermolysis Bullosa (QOLEB) questionnaire [ Time Frame: baseline up to12 months post treatment ]Descriptive methods used to analyze scores from QOLEB questionnaire. It consists of 17 questions with four response choices from "not at all" to "constant"
- Biomarker Analysis [ Time Frame: baseline up to12 months post treatment ]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.
- Efficacy of rigosertib sodium treatment: The Objective Response Rate [ Time Frame: baseline to end of treatment (52 weeks) ]The Objective Response Rate (ORR) will be computed with the corresponding exact binomial 90% confidence interval.
- Exosome sequencing [ Time Frame: baseline up to12 months post treatment ]whole exosome sequencing will be done on frozen tumor tissue. The investigators will catalogue somatic mutations identified in each tumor and compare these data with patient response and ex-vivo tumor responses.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04177498
|Contact: Neda Nikbakht, MD, PhDemail@example.com|
|United States, Pennsylvania|
|Sidney Kimmel Cancer Center at Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Neda Nikbakht, MD, PhD 215-503-4834 firstname.lastname@example.org|
|Principal Investigator:||Neda Nikbakht, MD, PhD||Sidney Kimmel Cancer Center at Thomas Jefferson University|