Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC

NCT04177498 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19G.527JT 13813
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  Defined as the proportion of patients who achieve either a complete response (CR) or partial response (PR)

  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.

  baseline up to12 months post treatment

Secondary Outcomes (3)

• Quality of Life Epidermolysis Bullosa (QOLEB) questionnaire

  baseline up to12 months post treatment

• Biomarker Analysis

  baseline up to12 months post treatment

• Efficacy of rigosertib sodium treatment: The Objective Response Rate

  baseline to end of treatment (52 weeks)

Other Outcomes (1)

• Exosome sequencing

  baseline up to12 months post treatment

Study Arms (1)

Treatment (rigosertib sodium)

EXPERIMENTAL

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; Other: Quality-of-Life Assessment

Interventions

Rigosertib Sodium DRUG

given PO or 72 hour continuous infusion

Also known as: ON 01910.Na

Treatment (rigosertib sodium)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (rigosertib sodium)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age;
• Diagnosis of RDEB associated unresectable, locally advanced or metastatic SCC of the skin confirmed prior to the Screening Visit.
• Failure to respond to SCC standard of care as follows; surgical excision, radiotherapy and conventional chemotherapy with e.g. platin derivates (i.e., cisplatin carboplatin) or cetuximab, 5-fluorouracil, bleomycin, methotrexate, adriamycin, taxanes, gemcitabine or ifosfamide alone or in combination; or failure to respond to previous alternative biologic treatments such as epidermal growth factor inhibitors (like cetuximab and panitumumab) or immune checkpoint (programmed cell death 1) inhibitors (such as nivolumab, pembrolizumab, cempilimab). For recent guidelines on standard of care for RDEB SCC and non EB-SCC
• Is not currently receiving any other cancer therapy.
• Measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.

You may not qualify if:

• Response to standard of care a. Surgical excision, radiotherapy and or conventional chemotherapy with e.g. platin derivates (i.e., cisplatin, carboplatin) or cetuximab, 5-fluorouracil, bleomycin, methotrexate, adriamycin, taxanes, gemcitabine or ifosfamide alone or in combination; or alternative biologic treatments such as epidermal growth factor inhibitors (like cetuximab and panitumumab) or immune checkpoint (programmed cell death 1) inhibitors (such as nivolumab, pembrolizumab, cempilimab). For recent guidelines on standard of care for RDEB SCC and non EB-SCC
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris
• Active systemic infection not adequately responding to appropriate therapy
• Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease, ≥5.3 mg/dL in patients if related to hemolysis or Gilbert's disease
• Alanine transaminase (ALT)/aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN)
• Serum creatinine ≥2 .0 mg/dL or eGFR (estimated Glomerular Filtration Rate) \<60 mL/min.
• White blood cell count ≤ 2000/μl OR Neutrophils ≤ 1500/μL OR Platelets ≤ 100 x103/μL OR Hemoglobin ≤ 7.9 g/dL
• Known active HIV, hepatitis B or hepatitis C, where active is defined as follows: a. HIV or Hepatitis C - presence of viral load b. Hepatitis B - antigen positive
• Uncorrected hyponatremia (defined as serum sodium value of \<125 mmol/L)
• Female patients of child-bearing potential and male patients with partners of childbearing potential who are unwilling to follow strict contraception requirements throughout the study, up to and including the 30-day non-treatment follow-up period
• Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use one or more reliable methods of contraception with a Pearl index ≤1 including combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (either oral or intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (either oral or injectable or implantable); an intrauterine device (IUD); an intrauterine hormone-releasing system ( IUS); bilateral tubal occlusion; vasectomised partner or sexual abstinence. Reliable contraception should be maintained throughout the study. A pregnancy test in urine will be performed at screening in all women of childbearing potential, and repeated before biopsy treatment and at all visits. Any postmenopausal women (physiologic menopause defined as "12 consecutive months of amenorrhea") or women permanently sterilized (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) will not be required to undergo pregnancy test.
• Uncontrolled hypertension a. (i.e. systolic blood pressure greater than or equal to 140mmHg and diastolic blood pressure greater than or equal to 90mmHg despite intake of ≥ 3 antihypertensive medications with complementary mechanisms of action (a diuretic should be 1 component)
• Patient is currently participating and receiving study therapy or systemic therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements
• Patients (or patient's legally authorized representative) unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Traws Pharma, Inc.: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Study Officials

• Neda Nikbakht, MD, PhD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 26, 2019
• Study Start: August 24, 2021
• Primary Completion: May 5, 2025
• Study Completion: May 5, 2025
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)