Rigosertib for RDEB-SCC

• Register: ClinicalTrials.gov
• Last refreshed on: 4 December 2023
• Main ID: NCT03786237
• Date of registration: 14/11/2018
• Prospective Registration: Yes
• Primary sponsor: Prof. Johann Bauer
• Public title: Rigosertib for RDEB-SCC
• Scientific title: A Phase II, Open Study to Assess Efficacy and Safety of Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated Locally Advanced/Metastatic Squamous Cell Carcinoma
• Date of first enrolment: April 12, 2021
• Target sample size: 12
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03786237
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Austria

Contacts

• Name: Manager EB Study Center

• Name: Elisabeth Mayr, PhD

• Name: Johann W Bauer, Prof., MD
• Affiliation: Department of Dermatology, Paracelsus Medical University, Salzburger Landeskliniken

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 18-79 years of age;

2. Diagnosis of unresectable, locally advanced or metastatic SCC confirmed prior to the
Screening Visit.

3. Failure to respond to RDEB SCC standard of care, such as surgical excision,
radiotherapy or conventional cytotoxic chemotherapy with e.g. platin derivates (i.e.

cisplatin or carboplatin), 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, cemiplimab). For recent guidelines on
standard of care for RDEB SCC and non EB-SCC please see Mellerio et al., 2016;
Stratigos et al., 2015 and Kim et al., 2018.

4. Is not currently receiving any other cancer therapy.

5. Measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

6. Patient (or patient's legally authorized representative) must have signed an informed

Exclusion Criteria

1. Response to standard of care.

2. Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure or unstable angina pectoris.

3. Active systemic infection not adequately responding to appropriate therapy.

4. Total bilirubin = 1.5 mg/dL (=5.3 mg/dL in patients if related to hemolysis or
Gilbert's disease).

5. Alanine transaminase (ALT)/aspartate transaminase (AST) = 2.5 x upper limit of normal
(ULN).

6. Serum creatinine =2 .0 mg/dL or eGFR (estimated Glomerular Filtration Rate) <60mL/min.

7. White blood cell count = 2000/µl, neutrophils = 1500/µL, platelets = 100 x103/µL,
hemoglobin = 7.9 g/dL.

8. 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

9. Uncorrected hyponatremia (defined as serum sodium value of <125 mmol/L).

10. Male patients with partners of child-bearing potential who are unwilling to use male
contraception (condom) throughout the study, up to and including the 30-day
nontreatment follow-up period.

11. 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 highly effective and reliable methods of contraception with a Pearl
index =1 including combined (estrogen and progestogen containing) hormonal
contraception associated with inhibition of ovulation (oral or intravaginal or
transdermal); progestogen-only hormonal contraception associated with inhibition of
ovulation (oral or injectable or implantable); an intrauterine device (IUD); an
intrauterine hormone-releasing system ( IUS); bilateral tubal occlusion; vasectomised
partner (provided that partner is the sole sexual partner of the WOCBP trial
participant and that the vasectomised partner has received medical assessment of the
surgical success) or sexual abstinence (The reliability of sexuality abstinence needs
to be evaluated in relation to the duration of the clinical trial and the preferred
and usual lifestyle of the subject). Reliable contraception should be maintained
throughout the study. A pregnancy test in serum will be performed at screening in all
women of childbearing potential, and in urine 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.

12. Uncontrolled hypertension. (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); (Whelton et al., 2018).

13. 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.

14. Psychiatric illness or social situation that would limit the patient's ability to
tolerate and/or comply with study requirements.

15. Patients (or parents in case of paediatric subject) 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.

16. History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the study, interfere with the patient's participation
for the full duration of the study, or is not in the best interest of the patient to
participate, in the opinion of the treating Investigator.

17. Known hypersensitivity reaction to any of the components of study treatment.

18. Presence of clinically significant ECG abnormalities based on the inverstigator´s
criteria.



Age minimum: 18 Years
Age maximum: 79 Years
Gender: All

Health Condition(s) or Problem(s) studied

Epidermolysis Bullosa Dystrophica

Squamous Cell Carcinoma

Intervention(s)

Drug: Rigosertib Oral Capsules / Rigosertib Intravenous

Primary Outcome(s)

Efficacy: Objective Response Rate (ORR) [Time Frame: 1 year]

Number of Treatment-related adverse events [Time Frame: 1 year]

Secondary Outcome(s)

Evaluation of quality of life using the "Quality of life in Epidermolysis bullosa questionnaire (QOLEB)" [Time Frame: 1 year]

Rate of presence or absence of cancer specific biomarkers [Time Frame: 1 year]

Secondary ID(s)

Rigosertib 4.0

Source(s) of Monetary Support

Please refer to primary and secondary sponsors