A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Kevetrin; Kevetrin
Intervention description: Kevetrin dose to associated cohort; Kevetrin dose to associated cohort
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Female
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      Cellceutix has developed Kevetrin (thioureidobutyronitrile), belonging to an
      anti-proliferative p53 activator pharmacological class, for the treatment of cancer.
      Nonclinical studies have demonstrated that Kevetrin induces apoptosis by activation of wild
      type p53 and induces apoptosis in mutant p53 cells by degradation of oncogenic mutant p53.

      In this Phase 2 study, two different short-term treatment regimens of Kevetrin will be
      evaluated for safety, tolerability, changes in biomarkers/objective tumor response, and to
      evaluate the pharmacokinetics of Kevetrin when administered to subjects with
      platinum-resistant/refractory ovarian cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Evidence of a personally signed and dated written informed consent to participate in
             the clinical study

          2. Non-pregnant female adults at least 18 years of age at time of informed consent

          3. Histologically confirmed serous epithelial ovarian cancer with peritoneal metastases

          4. Platinum resistant/refractory disease, defined as disease progression/relapse within 6
             months following the last administered dose of platinum therapy (resistant), or lack
             of response or disease progression while receiving the most recent platinum based
             therapy (refractory), respectively

          5. Measurable disease, as determined by radiologist evaluator, with at least 1
             unidimensional measurable lesion (target lesion) by RECIST v.1.1 that has not
             previously been irradiated or biopsied

          6. Presence of non-target lesions that have not previously been irradiated or biopsied;
             to allow for collection of needle-biopsies at Screening and after completion of
             Kevetrin treatment

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          8. Adequate hematologic and organ function as confirmed by laboratory values at
             Screening:

               1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 1500 Cells/μL (with no
                  evidence that this ANC was induced or supported by granulocyte colony stimulating
                  factors)

               2. Hemoglobin ≥ 9 g/dL (with no RBC transfusions within 7 days of Screening)

               3. Platelets ≥ 100,000 cells/μL (with no evidence that this platelet count was
                  induced or supported by a platelet-stimulating agent)

               4. Renal function: creatinine ≤ 1.5 x ULN

               5. Hepatic function: total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 3 x ULN; alkaline
                  phosphatase ≤ 2.5 x ULN

               6. Neurologic function: neuropathy (sensory and motor) ≤ CTCAE Grade 1

               7. Coagulation status: prothrombin time (PT) ≤ 1.5 ULN or INR within normal limits;
                  and partial thromboplastin time (PTT) ≤ 1.2 × ULN

          9. Women of child-bearing potential are required to use effective contraception
             throughout the study period. Effective contraception methods include:

               1. Total abstinence (if this is the usual lifestyle of the subject). Periodic
                  abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and
                  withdrawal are not acceptable methods of contraception. (Subject must agree to
                  use contraception should they become sexually active while on the study.)

               2. Surgical sterilization (hysterectomy and/or bilateral oophorectomy) or tubal
                  ligation at least six weeks before start of study treatment.

               3. Male partner sterilization, occurring at least 6 months prior to screening. For
                  female subjects on the study, the vasectomized male partner should be their sole
                  partner.

               4. Double barrier method: Condom or Occlusive cap (diaphragm or cervical/vault caps)
                  with spermicidal foam/gel/film/cream/vaginal suppository.

               5. Oral*/ injected/ implanted/ transdermal hormonal contraception or other forms of
                  hormonal contraception that have comparable efficacy (failure rate <1%), e.g.,
                  hormone vaginal ring.

               6. Intrauterine device or intrauterine system. *Stable oral contraception use (on
                  the same pill) for a minimum of 3 months before taking study treatment.

             Women are considered post-menopausal and not of child-bearing potential if they have
             had 12 consecutive months of natural (spontaneous) amenorrhea with an appropriate
             clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had
             surgical hysterectomy and/or bilateral oophorectomy or tubal ligation at least six
             weeks ago.

         10. Estimated life expectancy of at least 6 months, in the Investigator's opinion

         11. Willing and able to comply with scheduled visits, study assessments and laboratory
             tests, and other study procedures

        Exclusion Criteria:

          1. Unwilling to allow removal of tumor biological samples for analysis, i.e., biopsies of
             tumor lesions, and/or collection of ascites fluid from abdominal ascites (if present)

          2. Non epithelial tumor, including malignant mixed Müllerian tumors without high grade
             serous component, or ovarian tumors with low malignant potential (i.e., borderline
             tumors)

          3. Known presence of central nervous system metastases

          4. Presence of tumor metastases causing significant pleural disease/effusion unilaterally
             or bilaterally (significant pleural effusion is defined by need for thoracentesis more
             frequently than once every 21 days)

          5. Presence of ascites that requires paracentesis more frequently than once every 21
             days.

          6. A history of another primary cancer that has been active or treated within the past 3
             years prior to start of study treatment, with the exception of adequately
             treated/resected: basal cell or squamous cell skin carcinoma or actinic keratoses; or
             carcinoma in situ of the breast or of the cervix; or non-invasive malignant colon
             polyps

          7. Persistent toxic effects with severity of CTCAE grade 2 or greater (excluding
             alopecia) caused by previous treatment

          8. History of arterial or deep venous thromboembolism within the 12 months prior to
             enrollment

          9. Clinically significant cardiac disease, including:

               1. Myocardial infarction or unstable angina < 6 months prior to enrollment

               2. New York Heart Association (NYHA) Grade II or greater congestive heart failure

               3. Cardiac arrhythmia requiring medication (does not include asymptomatic atrial
                  fibrillation with controlled ventricular rate)

         10. Electrocardiogram (ECG) obtained at Screening which shows QTc prolongation or other
             medically relevant abnormalities which may affect subject safety or interpretation of
             study results

         11. At a higher than average risk, in the Investigator's opinion, of bowel perforation
             (e.g., symptoms of partial or complete bowel obstruction, recent (within 6 months)
             history of fistula or bowel perforation, requirement for total parenteral nutrition
             and continuous hydration)

         12. Active or chronic recurrent systemic infections that require continuous antimicrobial
             therapy during the Kevetrin study period

         13. Past medical history of infection with HIV, hepatitis B or hepatitis C

         14. Ongoing or recent history of any other uncontrolled and/or clinically significant
             systemic disease or condition which, in the Investigator's medical opinion, should
             exclude participation in the study

         15. Less than 3 weeks between major surgery and planned start of study treatment; major
             incisions must have healed

         16. Less than 4 weeks since last treatment for ovarian cancer

         17. Any investigational or experimental therapy or procedure or participation in any
             interventional trial within 4 weeks or 5 half-lives (whichever is longer) prior to
             start of study treatment

         18. Women of child-bearing potential who are pregnant or nursing (lactating)

         19. Previous participation in a clinical study of Kevetrin

         20. History of alcohol or substance abuse, unless in full remission for more than 6 months
             prior to start of study treatment

         21. Any other severe acute or chronic medical or psychiatric condition or test
             abnormality(ies) that, in the Investigator's opinion, puts the subject at significant
             risk, could confound the study results, or may interfere significantly with the
             subject's participation in the study