This pilot trial studies how rigsertib sodium works in treating patients with Recessive
Dystrophic Epidermolysis bullosa (RDEB) with locally advanced Squamous Cell Carcinoma (SCC).
Rigosertib may selectively target Epidermolysis bullosa (EB) cancer cells while leaving
normal EB cells unaffected.
PRIMARY OBJECTIVES:
I. To estimate the anti-tumor activity of oral or IV rigosertib in RDEB patients with
advanced SCC that have 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 by
RECIST v1.1 II. To evaluate the safety and tolerability of oral rigosertib administered
either orally daily 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
SECONDARY OBJECTIVES:
I. Assess impact on quality of life (QoL) II. Biomarker analysis (to include markers of
PI3K/Akt and PLK1 pathways) performed on all archival tissue from all patients
EXPLORATORY OBJECTIVE:
I. Exome sequencing of patient tumors before, during, and after treatment
OUTLINE: Patients will receive rigosertib sodium as either oral capsules or IV infusion. Mode
of application is determined by the responsible investigator depending on participant's
needs, general condition, and possibility of ambulatory treatment or need of hospitalization.
Patients will take oral rigosertib continuously for a total of three weeks of a four-week
cycle (three weeks on, one week off drug).
For IV treatment, patients will receive rigosertib IV 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.
Patients will receive treatment over a 52 week period. After completion of study treatment,
patients are followed periodically every 3 months over a 12 month period.
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).
