Rigosertib for RDEB-SCC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eb Haus Austria Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

completed 1 Dec 2025

Decision date (initial)

2024-12-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518846-25-00

EudraCT number

2016-003832-19

ClinicalTrials.gov

NCT03786237

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety and tolerability of Rigosertib
administered either orally daily for 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.
To estimate the anti-tumor activity of Rigosertib in RDEB
patients with advanced SCC that has 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.

Secondary objectives 2

1. Assess impact on quality of life (QOLEB).
2. Biomarker analysis (to include markers of PI3K/Akt and PLK1 pathways) performed on all archival tissue from all patients.

Conditions and MedDRA coding

Recessive Dystrophic Epidermolysis bullosa associated Locally Advanced/Metastatic Squamous Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of RDEB confirmed by genetic testing or by a skin biopsy with immunofluorescence mapping (IFM).
2. 18-79 years of age
3. Diagnosis of unresectable, locally advanced or metastatic SCC confirmed prior to the screening visit.
4. 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.
5. Is not currently receiving any other cancer therapy.
6. Measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
7. 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

Exclusion criteria 18

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) <60 mL/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 non-treatment follow-up period;
11. Female subjects: pregnant or lactating women and all women Rigosertib for RDEB-SCC Version 5.0; 15.09.2023 Confidential 9 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 (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 (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 sexual 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 repeated 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 investigator´s criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To determine the Objective Response Rate (ORR) of therapy with Rigosertib in RDEB patients with locally advanced/metastatic squamous cell carcinoma of the skin using Response Criteria in Solid Tumors Version 1.1 (RECIST1.1) per site assessment up to 52 weeks by CT/MR Scan.
2. To evaluate the safety and tolerability of Rigosertib administered either orally as capsules or dissolved capsules daily for three weeks on, one week off or IV as a 72- hr CIV 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.

Secondary endpoints 2

1. Assess impact on quality of life (QOLEB).
2. Biomarker analysis (to include markers of PI3K/Akt and PLK1 pathways) performed on all archival tissues from all patients.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eb Haus Austria Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Sponsor organisation

Eb Haus Austria Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Address

Muellner Hauptstrasse 48

City

Salzburg

Postcode

5020

Country

Austria

Scientific contact point

Organisation

Eb Haus Austria Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Contact name

EB Haus Study Centre

Public contact point

Organisation

Eb Haus Austria Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH

Contact name

EB Haus Study Centre

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications