Rigosertib for Skin Cancer in Dystrophic Epidermolysis Bullosa

Overseen By Neda Nikbakht, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Thomas Jefferson University

Disqualifiers: Uncontrolled illness, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how rigosertib sodium can help individuals with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who also have Squamous Cell Carcinoma (SCC), a form of skin cancer. The researchers aim to determine if rigosertib can target and attack cancer cells without harming surrounding healthy cells. Suitable candidates have RDEB with advanced SCC and have not responded to standard treatments like surgery or chemotherapy. Participants will receive rigosertib either orally or through an IV for up to 52 weeks, with breaks between treatment cycles. As an Early Phase 1 trial, this research focuses on understanding how rigosertib works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other cancer therapy while participating.

Is there any evidence suggesting that rigosertib sodium is likely to be safe for humans?

Research suggests that rigosertib sodium could be a promising treatment for skin cancer in individuals with Recessive Dystrophic Epidermolysis Bullosa (RDEB). However, specific safety information for rigosertib is not yet available in existing studies.

The current study is in an early phase, so researchers are closely monitoring safety and side effects. This stage primarily assesses how well participants tolerate the treatment, but specific results are not yet available.

Rigosertib is designed to target cancer cells specifically, potentially protecting normal cells from harm. This targeted approach shows promise, but further research is needed to confirm its safety. Always consult a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer in Dystrophic Epidermolysis Bullosa, which often involve surgical options or topical therapies, Rigosertib Sodium stands out as an innovative option due to its unique mechanism of action. It targets cancer cells by inhibiting the RAS signaling pathway, which is crucial in cell growth and division. Additionally, it can be administered both orally and intravenously, providing flexibility in treatment approaches. Researchers are excited because this targeted approach might offer more effective results with potentially fewer side effects compared to conventional treatments.

What evidence suggests that rigosertib sodium might be an effective treatment for skin cancer in RDEB?

Research shows that rigosertib sodium, the treatment under study in this trial, may help patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who have advanced Squamous Cell Carcinoma (SCC). In lab studies, rigosertib killed cancer cells in this condition without harming normal skin cells, indicating it targets cancer cells while sparing healthy ones. There is a significant need for effective treatments for RDEB-SCC, and rigosertib could be a valuable option. Early results suggest it might help manage this rare and challenging skin cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Neda Nikbakht, MD, PhD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who have Squamous Cell Carcinoma (SCC) that hasn't improved after standard treatments. Participants must not be on other cancer therapies, should understand the study and agree to participate, and need measurable SCC based on certain criteria. Pregnant women, those with active infections like HIV or hepatitis, uncontrolled health issues, or abnormal lab results can't join.

Inclusion Criteria

You have a tumor that can be measured according to specific guidelines.

Patient (or patient's legally authorized representative) must have signed an informed consent document indicating understanding and willingness to participate in the study

I have been diagnosed with a specific type of skin cancer that cannot be surgically removed.

Exclusion Criteria

Your blood test results show abnormal levels of bilirubin, liver enzymes, creatinine, white blood cells, neutrophils, platelets, or hemoglobin.

Unlikely to comply with the study protocol or unable to understand the nature and scope of the study

I am not pregnant or breastfeeding and use reliable birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rigosertib sodium either orally or via IV infusion over a 52-week period. Oral administration is three weeks on, one week off per cycle. IV administration is a 72-hour continuous infusion on Days 1-3 of a 2-week cycle for the first eight cycles, then on Days 1-3 of a 4-week cycle thereafter.

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with periodic follow-ups every 3 months over a 12-month period.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Rigosertib Sodium

Trial Overview The trial is testing how well rigosertib sodium works in treating patients with advanced skin cancer associated with RDEB. The goal is to see if rigosertib targets cancer cells without harming normal cells. Patients' quality of life will also be assessed during the study.

How Is the Trial Designed?

Group I: Treatment (rigosertib sodium) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Traws Pharma, Inc.

Industry Sponsor

Trials

34

Recruited

1,800+

Onconova Therapeutics, Inc.

Industry Sponsor

Trials

32

Recruited

1,700+

Published Research Related to This Trial

Topical RTA 408 (Omaveloxolone) significantly reduced the severity of skin symptoms in a mouse model of epidermolysis bullosa (EB) and inhibited squamous cell carcinoma (SCC) growth without causing toxicity.

In laboratory studies, RTA 408 decreased cell viability in SCC cell lines associated with EB, suggesting its potential as a dual anti-inflammatory and anti-cancer treatment for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model. Cohen-Nowak, AJ., Cohen, AJ., Correia, ED., et al.[2022]

Cetuximab, an epidermal growth factor receptor antagonist, was successfully used to treat metastasized cutaneous squamous cell carcinoma (SCC) in a patient with generalized recessive dystrophic epidermolysis bullosa (RDEB), showing a favorable response.

The treatment was well-tolerated, with adverse events comparable to those in patients without EB, and importantly, there were no additional negative effects on the skin, such as increased blistering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab therapy of metastasizing cutaneous squamous cell carcinoma in a patient with severe recessive dystrophic epidermolysis bullosa. Arnold, AW., Bruckner-Tuderman, L., Zuger, C., et al.[2018]

In two patients with advanced squamous cell carcinoma associated with dystrophic epidermolysis bullosa, cisplatin-based chemotherapy was administered without significant cutaneous toxicity, suggesting a potential treatment option for this high-risk population.

This case highlights the possibility of using systemic chemotherapy in patients with severe skin conditions, where traditional treatments are often avoided due to concerns about severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Squamous cell carcinoma in epidermolysis bullosa. Treatment with systemic chemotherapy. Lentz, SR., Raish, RJ., Orlowski, EP., et al.[2019]

Targeted anticancer therapies have led to significant changes in oncology patient management, but they often come with cutaneous adverse effects that can limit treatment effectiveness or lead to therapy discontinuation.

Specific side effects vary by drug class: tyrosine kinase inhibitors can cause rashes and hand-foot reactions, while epidermal growth factor receptor inhibitors may lead to papulopustular rashes and hair changes, highlighting the need for careful monitoring of skin reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin Manifestations of Targeted Antineoplastic Therapy. Sanmartín, O.[2018]

The spliceosome-mediated RNA trans-splicing (SMaRT) approach using RTM44 effectively targeted and modified cancer cells in a skin cancer model associated with recessive dystrophic epidermolysis bullosa (RDEB), demonstrating specificity in killing tumor cells while sparing normal cells.

Treatment with the prodrug ganciclovir (GCV) in mice with RTM44-expressing cancer cells led to a significant reduction in tumor volume and weight, indicating the potential efficacy of this targeted therapy in aggressive skin cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating a Targeted Cancer Therapy Approach Mediated by RNA trans-Splicing In Vitro and in a Xenograft Model for Epidermolysis Bullosa-Associated Skin Cancer. Woess, K., Sun, Y., Morio, H., et al.[2022]

Inhibitors targeting the RAS-RAF-MEK-ERK pathway, such as vemurafenib, have shown efficacy in treating various tumors, including late-stage melanoma, and are generally considered safe but can cause significant cutaneous side effects.

Common skin toxicities associated with these therapies include rashes, palmoplantar erythrodysesthesia, and photosensitivity, which can often be managed with conservative treatments, but clinicians should be vigilant for the development of skin tumors like keratoacanthomas during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management. Manousaridis, I., Mavridou, S., Goerdt, S., et al.[2022]

Rigosertib functions as a RAS mimetic, which means it mimics the action of RAS proteins by binding to their RAS-binding domain on various effector proteins.

This mechanism of action suggests that rigosertib could potentially interfere with RAS signaling pathways, which are often implicated in cancer, making it a candidate for cancer treatment research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of RAS-Binding Domain Interactions Inhibits RAS Signaling. [2017]

In a study of 53 GIST patients treated with sunitinib, those with hand-foot skin reaction (HFSR) showed significantly elevated levels of soluble FasL (sFasL) in their plasma and skin lesions, indicating a potential mechanism for the skin toxicity associated with the drug.

The research demonstrated that the interaction between Fas and FasL leads to keratinocyte death, which is responsible for the skin damage seen in HFSR, suggesting that targeting this pathway could help mitigate these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fas/Fas ligand mediates keratinocyte death in sunitinib-induced hand-foot skin reaction. Yeh, CN., Chung, WH., Su, SC., et al.[2021]

Cetuximab, an EGFR-targeting monoclonal antibody, has been used to treat patients with dystrophic epidermolysis bullosa (DEB) and aggressive squamous cell carcinomas (SCC), showing promising results with mild side effects.

The study suggests that administering cetuximab early in the treatment of DEB-related SCC may enhance its effectiveness, as EGFR is often expressed in these tumors, although expression levels can vary among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR inhibition for metastasized cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa. Diociaiuti, A., Steinke, H., Nyström, A., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03786237

Study Details | NCT03786237 | Rigosertib for RDEB-SCC The investigators have identified that rigosertib most selectively kills EB cancer cells in vitro while leaving normal EB skin cells unaffected. This project ...

2. jdc.jefferson.edu jdc.jefferson.edu/cgi/viewcontent.cgi?article=1233&context=dcbfp

Efficacy and Safety of Rigosertib in Patients With Recessive ... Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic.

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04177498/

Clinical Trial: NCT04177498 This pilot trial studies how rigsertib sodium works in treating patients with Recessive Dystrophic Epidermolysis bullosa (RDEB) with locally ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40439508/

Efficacy and safety of rigosertib in patients with recessive ... Conclusions: These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, ...

5. withpower.com withpower.com/trial/early-phase-1-epidermolysis-bullosa-7-2021-aba4f

Rigosertib for Skin Cancer in Dystrophic Epidermolysis ... This trial studies how rigosertib sodium, a drug taken orally or through IV, can help treat patients with a rare skin condition and advanced skin cancer who ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04177498?term=nci%20c%2001910&viewType=Table&checkSpell=&rank=1

Study Details | NCT04177498 | Rigosertib in Patients With ... Rigosertib may selectively target Epidermolysis bullosa (EB) cancer cells while leaving normal EB cells unaffected.