Clinical trial NCT03042702
Conditions: Ovarian Cancer
Sponsor: Innovation Pharmaceuticals, Inc.
Start date: 2017-02-09; Completion date: 2017-11-10
Enrollment: 2 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief 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.

Detailed description:
This is an open label, dose-escalation trial to study the safety, biomarker changes (including modulation of p53), objective tumor response changes, and pharmacokinetics following administration of two different treatment regimens of Kevetrin over a 3-week period to subjects with platinum-resistant/refractory ovarian cancer. Following the 3 weeks of Kevetrin dosing, subjects are to be followed up for 3 weeks after completion of Kevetrin treatment. Standard of care treatment, as medically appropriate and per local guidelines, outside of this study protocol can commence after the collection of the post-Kevetrin treatment biomarker samples (collected on Day 21±1 day). The patient population recruited into this study includes those ovarian cancer patients that have 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. Patients may or may not have had additional treatment (e.g., Doxil) prior to entry in this study.

A total of approximately 10 study participants are planned to be enrolled in two cohorts of approximately 5 subjects per cohort, with enrollment in a sequential, dose-escalating fashion. Investigators and subjects will be aware of the treatment cohort into which they are recruiting. Cohort details and the planned doses are:

Cohort 1 (n=5) Kevetrin Cycle - Kevetrin 250 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week (750 mg/m2 per week), for 3 weeks (single cycle; total 9 doses); Follow-up for 3 weeks after Kevetrin treatment ends Cohort 2 (n=5) Kevetrin Cycle - Kevetrin 350 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week (1050 mg/m2 per week), for 3 weeks (single cycle; total 9 doses); Follow-up for 3 weeks after Kevetrin treatment ends Cohorts 1 and 2 will be conducted in a sequential fashion, with safety data from cohort 1 evaluated by an independent Data Monitoring Committee (DMC). The DMC will make appropriate recommendations based on the available safety data as regards the intent of progressing to the higher dose cohort 2.

Arms: arm 1: Kevetrin 250 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week (750 mg/m2 per week), for 3 weeks (single cycle; total 9 doses) Follow-up For 3 weeks after Kevetrin treatment ends arm 2: Kevetrin 350 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week (1050 mg/m2 per week), for 3 weeks (single cycle; total 9 doses) Follow-up For 3 weeks after Kevetrin treatment ends
Interventions: intervention 1: Kevetrin intervention 2: Kevetrin
Intervention descriptions: intervention 1: Kevetrin dose to associated cohort intervention 2: Kevetrin dose to associated cohort

Protocol documents:
Prot_SAP_000.pdf: 
CLINICAL PROTOCOL 
CTIX-KEV-201 
A Phase 2 study of Kevetrin (thioureidobutyronitrile) in Subjects with Platinum-
Resistant/Refractory Ovarian Cancer 
Document type: 
Clinical Protocol 
Version number: 
1.0 
Version date: 
08 December 2016 
CONFIDENTIALITY STATEMENT 
The information provided in this document is strictly confidential. This information may not 
be used, published or disclosed without prior written approval from Cellceutix. 
NCT:
NCT03042702


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PROTOCOL SYNOPSIS 
Name of Sponsor/Company: Cellceutix Corporation 
Name of Finished Product: Kevetrin  
Name of Active Ingredient: Thioureidobutyronitrile 
Title of Study:  
A Phase 2 study of Kevetrin (thioureidobutyronitrile) in Subjects with Platinum-
Resistant/Refractory Ovarian Cancer 
Study Centers:  
Approximately 3 sites in the United States 
Number of Subjects Planned:  
Approximately 10 study participants with platinum-resistant/refractory ovarian cancer 
Study Duration per subject:  
Approximately 10 weeks: 4 weeks for screening, a 3-week Kevetrin cycle, followed by a 
3-week follow-up 
Phase of Development:  
Phase 2  
Primary Objective(s):  
• To evaluate safety and tolerability of two different treatment regimens of Kevetrin 
when administered to subjects with platinum-resistant/refractory ovarian cancer 
• To evaluate changes in biomarkers and molecular signatures related to cell 
proliferation and cell death from tumor tissue, ascites fluid, and peripheral blood after 
treatment with Kevetrin to subjects with platinum-resistant/refractory ovarian cancer 
Secondary Objectives:  
• To evaluate the objective tumor response to treatment with Kevetrin when 
administered to subjects with platinum-resistant/refractory ovarian cancer 
• To evaluate the pharmacokinetics of Kevetrin after administration to subjects with 
platinum-resistant/refractory ovarian cancer 
Design and Methodology:  
This is an open label, dose-escalation trial to study the safety, biomarker changes 
(including modulation of p53), objective tumor response changes, and pharmacokinetics 
following administration of two different treatment regimens of Kevetrin over a 3-week 
period to subjects with platinum-resistant/refractory ovarian cancer. Following the 3 
weeks of Kevetrin dosing, subjects are to be followed up for 3 weeks after completion of 
Kevetrin treatment. Standard of care treatment, as medically appropriate and per local 


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guidelines, outside of this study protocol can commence after the collection of the post-
Kevetrin treatment biomarker samples (collected on Day 21±1 day). 
The patient population recruited into this study includes those ovarian cancer patients that 
have 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. Patients may or may not have had additional treatment (e.g., 
Doxil) prior to entry in this study.  
A total of approximately 10 study participants are planned to be enrolled in two cohorts of 
approximately 5 subjects per cohort, with enrollment in a sequential, dose-escalating 
fashion. Investigators and subjects will be aware of the treatment cohort into which they 
are recruiting. Cohort details and the planned doses are listed below: 
 
Cohort 1 (n=5) Kevetrin Cycle 
Kevetrin 250 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per 
week (750 mg/m2 per week), for 3 weeks (single cycle; total 9 doses) 
 
Follow-up 
For 3 weeks after Kevetrin treatment ends 
 
 
Cohort 2 (n=5) Kevetrin Cycle 
Kevetrin 350 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per 
week (1050 mg/m2 per week), for 3 weeks (single cycle; total 9 doses) 
 
Follow-up 
For 3 weeks after Kevetrin treatment ends 
Cohorts 1 and 2 will be conducted in a sequential fashion, with safety data from cohort 1 
evaluated by an independent Data Monitoring Committee (DMC). The DMC will make 
appropriate recommendations based on the available safety data as regards the intent of 
progressing to the higher dose cohort 2. 
Study Design Schematic 
 
If 2 of the 5 subjects in cohort 1 experience a dose-limiting toxicity (DLT) adverse event, 
the DMC will consider reducing the Kevetrin dose regimen for cohort 2 by 25%. 


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Dependent on the DLT adverse events experienced, the dose in cohort 1 may be repeated, 
or reduced. If no new or unexpected safety concerns are identified by the DMC safety 
review, enrollment of subjects to cohort 2 with a higher dose regimen of Kevetrin will 
commence. 
If a subject experiences a DLT adverse event during treatment with Kevetrin, treatment 
with Kevetrin will be stopped and the subject will be appropriately followed-up to 
document the course of the abnormality until returned to a normal or baseline level, or 
until the adverse event/abnormality is deemed clinically stable. For any DLT adverse 
event, the Investigator must immediately notify the Medical Monitor by telephone and 
follow-up in writing. 
For this study, a DLT adverse event is defined as follows, according to the NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03:  
Hematologic toxicity: 
• Grade 3 or 4 febrile neutropenia or Grade 4 neutrophil count decreased of ≥ 7 days’ 
duration 
• Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated by hemorrhage 
Nonhematologic toxicity: 
• Any grade ≥ 3 nonhematologic toxicity unless there is clear alternative evidence that 
the adverse event was not caused by Kevetrin 
• Grade 3 diarrhea, nausea, or vomiting may be excluded from DLT classification 
provided that the maximum time limit for supportive measures is 48 hours 
A subject studied under this clinical protocol will commence with a screening period of up 
to 4 weeks, a treatment cycle with Kevetrin (3 weeks), followed by a 3-week follow-up. 
Safety and tolerability will be assessed by ascertainment of AEs, physical examinations, 
and results of clinical laboratory testing, and vital signs assessments. Tumor measurement 
assessments, by computed tomography (CT) scan, will be taken pre- and post-Kevetrin 
treatment. Tumor biopsies and ascites fluid (if available), and blood samples for 
biomarkers will also be collected pre- and post-Kevetrin treatment. Serial blood samples 
for determination of plasma Kevetrin concentrations will be collected on Study Days 1 
and 5, from 2 hours pre-infusion out to 24 hours post-infusion completion. 
Any discontinuation of study treatment (Kevetrin) is to be reported by the Investigator to 
the Medical Monitor. Any subject that discontinues study treatment is to be followed up 
for (approximately) 3 weeks after the end of treatment. Subjects who withdraw from the 
study or discontinue treatment for reasons other than a demonstrated intolerance to 
Kevetrin or a DLT may trigger additional subjects to be enrolled, to obtain 5 completed 
subjects in each cohort. 
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 


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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: 
a. 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)   
b. Hemoglobin ≥ 9 g/dL (with no RBC transfusions within 7 days of Screening) 
c. Platelets ≥ 100,000 cells/μL (with no evidence that this platelet count was induced 
or supported by a platelet-stimulating agent) 
d. Renal function: creatinine ≤ 1.5 x ULN 
e. Hepatic function: total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 3 x ULN; alkaline 
phosphatase ≤ 2.5 x ULN 
f. Neurologic function: neuropathy (sensory and motor) ≤ CTCAE Grade 1 
g. 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: 
a. 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.) 
b. Surgical sterilization (hysterectomy and/or bilateral oophorectomy) or tubal 
ligation at least six weeks before start of study treatment.  
c. 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. 


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d. Double barrier method: Condom or Occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/vaginal suppository. 
e. Oral*/ injected/ implanted/ transdermal hormonal contraception or other forms of 
hormonal contraception that have comparable efficacy (failure rate <1%), e.g., 
hormone vaginal ring. 
f. 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: 


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a. Myocardial infarction or unstable angina < 6 months prior to enrollment 
b. New York Heart Association (NYHA) Grade II or greater congestive heart failure 
c. 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 
Test Product, Dose, and Mode of Administration: 
Kevetrin (thioureidobutyronitrile) will be supplied by the Sponsor in 5 mL glass vials, with 
each vial containing 200 mg Kevetrin (lyophilized). 
Kevetrin will be reconstituted in water for injection (WFI) and placed in a non-PVC infusion 
bag containing 250mL of 0.9% Sodium Chloride Injection USP (Braun L8002 or equivalent, 
provided by the site). A low sorbing (PVC-free) IV infusion set equipped with an in-line 


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0.2-µm pore size filter (CareFusion / Alaris 11532269 or equivalent, provided by the site) 
will be attached to the non-PVC bag.  
Cohort 1: Kevetrin 250 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week 
(750 mg/m2 per week), for 3 weeks 
Cohort 2: Kevetrin 350 mg/m2 IV per dose every other day (q.o.d.)/ 3 doses per week 
(1050 mg/m2 per week), for 3 weeks 
Nine (9) doses of Kevetrin are to be divided and administered every other day (q.o.d.) as 
three doses split over each 7-day period, for a single (21-day) treatment cycle.  
Doses 1, 2, and 3 are each separated by approximately 48 hours; Dose 4 is administered 
approximately 72 hours after Dose 3. Doses 5 and 6, and doses 8 and 9 are administered 
approximately 48 hours after doses 4 and 7, respectively. The separation between doses 6 
and 7 is approximately 72 hours. 
Each Kevetrin dose is to be administered intravenously over a duration of no less than 180 
minutes (3 hours). A pre-medication regimen is recommended for administration within 30 
to 60 minutes prior to initiation of each Kevetrin infusion. 
Data Analysis: 
Details of the statistical methodology for summary and analyses of the data collected in this 
study will be prepared separately from this protocol in a statistical analysis plan (SAP).  
All statistical analyses will be performed using SAS version 9.3 or higher.  
Safety endpoints: AEs, SAEs, dosing compliance, any discontinuations from Kevetrin 
treatment due to toxicities, and changes in laboratory values, vital signs, ECGs, and ECOG 
performance status, and incidence of clinical laboratory, blood pressure, heart rate, 
temperature and respiration rate, and ECG abnormalities. 
Biomarker endpoints: 
• Change from baseline in tumor tissue markers and/or cellular markers (in cells 
separated from ascites fluid) including, but not limited to, changes in transcriptional 
and translational pathways leading to anticancer activitiy such as p53signaling 
pathway, miRNA-34a, and other tumor activity markers. 
• Change from baseline in ascites fluid markers and/or plasma markers, including 
CA-125, CCL2, miRNA-25, miRNA-27a, and miRNA-1274b. 
Tumor measurement endpoints:  
• Number of subjects in each RECIST response category (complete response, partial 
response, stable disease or progressive disease) 
• Number of subjects with confirmed objective tumor response according to RECIST 
• Change from baseline in tumor size (defined as sum of the longest diameters as 
measured among all target lesions) 
All safety data, demographic and baseline characteristics, will be summarized descriptively 
through appropriate data tabulations, descriptive statistics, and categorical summaries. 


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Biomarker and tumor measurement endpoints will be summarized with descriptive statistics 
by cohort and visit. Summary statistics for continuous variables will include N, mean, 
standard deviation, minimum, median, maximum. Summary statistics for discrete variables 
will be presented in contingency tables and will include absolute and relative frequencies.  
Pharmacokinetic parameters will be estimated from those subjects with a sufficient number 
of plasma concentrations to allow for such estimation. 
Interim analyses may be conducted to support decision making concerning the current 
clinical study, the Sponsor’s clinical development projects in general or in case of any safety 
concerns. As this is an open label study, safety and efficacy data (individual and aggregate) 
will be reviewed by the Sponsor on an ongoing basis throughout the study. 
A planned interim analyses for investigating safety will be conducted after completion of 
cohort 1. Safety data will be provided to an independent DMC for review. The DMC will 
make appropriate recommendations based on the available safety data as regards the intent 
of progressing to the higher dose cohort 2. A full review by the Sponsor of all data from 
participants in cohort 1 after cohort completion will also be conducted.