Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC

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Brief Title

Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC

Official Title

A Pilot, Open Study to Assess Efficacy and Safety of Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated Locally Advanced/Metastatic Squamous Cell Carcinoma

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Overall Response Rate (ORR)

Secondary Outcome

 Quality of Life Epidermolysis Bullosa (QOLEB) questionnaire

Condition

Recessive Dystrophic Epidermolysis Bullosa

Intervention

Rigosertib Sodium

Study Arms / Comparison Groups

 Treatment (rigosertib sodium)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

6

Start Date

August 24, 2021

Completion Date

June 2023

Primary Completion Date

June 2023

Eligibility Criteria

        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).
      

Gender

All

Ages

18 Years - 79 Years

Accepts Healthy Volunteers

No

Contacts

Neda Nikbakht, MD, PhD, 215-503-4834, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04177498

Organization ID

19G.527


Responsible Party

Sponsor

Study Sponsor

Thomas Jefferson University

Collaborators

 Onconova Therapeutics, Inc.

Study Sponsor

Neda Nikbakht, MD, PhD, Principal Investigator, Sidney Kimmel Cancer Center at Thomas Jefferson University


Verification Date

August 2021