Rigosertib for RDEB-SCC
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|ClinicalTrials.gov Identifier: NCT03786237|
Recruitment Status : Not yet recruiting
First Posted : December 24, 2018
Last Update Posted : April 4, 2019
Epidermolysis bullosa (EB) is a heritable skin disease characterized by marked fragility of epithelialized tissue with blistering in skin and mucous membranes following the slightest mechanical trauma. Eighty percent of all patients suffering from recessive dystrophic EB (RDEB), a subtype originating from mutations in the COL7A1 gene, develop squamous cell carcinoma (SCC). In RDEB patients SCC presents early (most patients are in their 20s or 30s) and shows a highly aggressive metastatic course which often leads to premature death at this young age.
In light of scarce data on the efficacy and safety of systemic treatment regimens for advanced SCC, the investigators propose to perform a small, "first in EB " trial of an experimental drug called rigosertib for the treatment of EB cancer. The trial will be conducted in two study centres, in London and Salzburg, and will last approximately 2.5 years with each patient recruited being in the study for 1 year. The drug is a polo-like kinase inhibitor interfering with different molecular pathways that are essential for cancer cell growth. Rigosertib was developed by Onconova Therapeutics and is currently tested in several clinical trials for a number of other cancers including myelodysplastic syndrome (a cancer of the blood). The investigators have identified that rigosertib most selectively kills EB cancer cells in vitro while leaving normal EB skin cells unaffected. This project will evaluate whether rigosertib is capable of inducing an anti-cancer response in EB patients and whether the drug is well-tolerated. Mechanisms of molecular targeting of squamous cancer cells by rigosertib will further be investigated in EB patients, also aiming at the identification of biomarkers that may allow the predictive identification of best responders.
|Condition or disease||Intervention/treatment||Phase|
|Epidermolysis Bullosa Dystrophica Squamous Cell Carcinoma||Drug: Rigosertib Oral Capsules / Rigosertib Oral Liquid Solution / Rigosertib Intravenous||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Estimated Study Start Date :||May 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||June 2021|
|Experimental: Treatment Oral Capsules / Oral liquid Solution / Intravenous||
Drug: Rigosertib Oral Capsules / Rigosertib Oral Liquid Solution / Rigosertib Intravenous
Patients will take Rigosertib either as oral capsules or oral liquid solution or will get intravenous infusions depending on the needs of the patients.
Oral Capsules/ Liquid Solution:
Patients will take oral Rigosertib continuously for a total of three weeks, every four week cycle (three weeks on, one week off drug) for up to 13 cycles. Patients will take 560 mg of oral Rigosertib (ie, 2 capsules of 280 mg or 7,47mL of the concentrate in 30mL water) in the morning and 280 mg of oral Rigosertib (ie, 1 capsule of 280 mg or 3,73mL of the concentrate in 30mL water) in the afternoon, total of 840mg/day.
For IV treatment Rigosertib 1800 mg/24 hr is diluted in 0.9% sodium chloride for injection just prior to dosing and is administered 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.
- Efficacy: Objective Response Rate (ORR) [ Time Frame: 1 year ]The primary (efficacy) objective of this trial is 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.
- Number of Treatment-related adverse events [ Time Frame: 1 year ]Safety will be evaluated for all treated patients, who receive at least one dose of Rigosertib, using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (http://ctep.cancer.gov). Safety assessments will be based on number of treatment related adverse events per grade.
- Evaluation of quality of life using the "Quality of life in Epidermolysis bullosa questionnaire (QOLEB)" [ Time Frame: 1 year ]Assess impact on quality of life using an Epidermolysis bullosa (EB) specific questionnaire developed and published by Murrell et al.2009. Total score is reported (range 0-75; 0 means EB has no affect on ones life, the higher the score the more affect and annoyance/handicap)
- Rate of presence or absence of cancer specific biomarkers [ Time Frame: 1 year ]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.
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): NCT03786237
|Contact: Manager EB Study Center||+43 5 7255 ext 82413||Clinical-Trialemail@example.com|
|Contact: Elisabeth Mayr, PhD||+43 5 7255 ext firstname.lastname@example.org|
|Principal Investigator:||Johann W Bauer, Prof., MD||Department of Dermatology, Paracelsus Medical University, Salzburger Landeskliniken|