A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer

This is an interventional treatment trial for Ovarian Cancer Read More

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