Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC

This is an interventional treatment trial for Recessive Dystrophic Epidermolysis Bullosa Read More

Inclusion Criteria:

1. 18-79 years of age;
2. Diagnosis of RDEB associated unresectable, locally advanced or metastatic SCC of the skin confirmed prior to the Screening Visit.
3. 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
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 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:

1. 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
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 not related to hemolysis or Gilbert's disease, ≥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 OR Neutrophils ≤ 1500/μL OR Platelets ≤ 100 x103/μL OR 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. 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
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 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.
12. 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)
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 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.
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. Any patient with a known medical condition leading to abnormal vital signs that is not correctable or a patient whose vital sign is within abnormal range upon arrival in clinic will not be receiving the medication. If this abnormal vital signs are not medically controlled and addressed that patient will be excluded at anytime (regardless of it is at arrival or in the middle of the study).