A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer

NCT03042702 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CTIX-KEV-201
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events

  Reporting of Adverse Events, and severity of adverse events

  6 Weeks

• Number of Participants With Changes in Biomarkers

  Changes in RNA and/or protein level of pre-specified biomarkers associated with the p53 signalling pathway and apoptosis will be compared between pre-treatment sample (tumor biopsy, ascites fluid, and peripheral blood) and post-treatment sample (tumor biopsy, ascites fluid, and peripheral blood)

  3 Weeks

Secondary Outcomes (4)

• Number of Participants by RECIST Tumor Response Category

  3 Weeks

• Maximum Plasma Concentration of Kevetrin (Cmax) on Days 1 and 5

  Prior to dosing, During 3h infusion: 60(±5) min, 120(±5) min, and 2 min prior to end of infusion, i.e., 178 min. Post infusion: 0.5 hour (±5 min), 1 hour (±5 min), 2 hour (±5 min), 4 hour (±10 mins), 6 hour (±30 mins) [optional], and 24(±4) hour

• Time to Reach the Maximum Plasma Concentration of Kevetrin (Tmax) on Days 1 and 5

  Prior to dosing, During 3h infusion: 60(±5) min, 120(±5) min, and 2 min prior to end of infusion, i.e., 178 min. Post infusion: 0.5 hour (±5 min), 1 hour (±5 min), 2 hour (±5 min), 4 hour (±10 mins), 6 hour (±30 mins) [optional], and 24(±4) hour

• Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUCt) on Days 1 and 5

  Prior to dosing, During 3h infusion: 60(±5) min, 120(±5) min, and 2 min prior to end of infusion, i.e., 178 min. Post infusion: 0.5 hour (±5 min), 1 hour (±5 min), 2 hour (±5 min), 4 hour (±10 mins), 6 hour (±30 mins) [optional], and 24(±4) hour

Study Arms (2)

Kevetrin 250 mg/m2 IV Cohort 1

EXPERIMENTAL

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

Drug: Kevetrin

Kevetrin 350 mg/m2 IV Cohort 2

EXPERIMENTAL

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

Drug: Kevetrin

Interventions

Kevetrin DRUG

Kevetrin dose to associated cohort

Also known as: Cohort

Kevetrin 250 mg/m2 IV Cohort 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of a personally signed and dated written informed consent to participate in the clinical study
• Non-pregnant female adults at least 18 years of age at time of informed consent
• Histologically confirmed serous epithelial ovarian cancer with peritoneal metastases
• 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
• 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
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic and organ function as confirmed by laboratory values at Screening:
• 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)
• Hemoglobin ≥ 9 g/dL (with no RBC transfusions within 7 days of Screening)
• Platelets ≥ 100,000 cells/μL (with no evidence that this platelet count was induced or supported by a platelet-stimulating agent)
• Renal function: creatinine ≤ 1.5 x ULN
• Hepatic function: total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 3 x ULN; alkaline phosphatase ≤ 2.5 x ULN
• Neurologic function: neuropathy (sensory and motor) ≤ CTCAE Grade 1
• Coagulation status: prothrombin time (PT) ≤ 1.5 ULN or INR within normal limits; and partial thromboplastin time (PTT) ≤ 1.2 × ULN

You may not qualify if:

• 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)
• Non epithelial tumor, including malignant mixed Müllerian tumors without high grade serous component, or ovarian tumors with low malignant potential (i.e., borderline tumors)
• Known presence of central nervous system metastases
• 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)
• Presence of ascites that requires paracentesis more frequently than once every 21 days.
• 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
• Persistent toxic effects with severity of CTCAE grade 2 or greater (excluding alopecia) caused by previous treatment
• History of arterial or deep venous thromboembolism within the 12 months prior to enrollment
• Clinically significant cardiac disease, including:
• Myocardial infarction or unstable angina \< 6 months prior to enrollment
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• Cardiac arrhythmia requiring medication (does not include asymptomatic atrial fibrillation with controlled ventricular rate)
• Electrocardiogram (ECG) obtained at Screening which shows QTc prolongation or other medically relevant abnormalities which may affect subject safety or interpretation of study results
• 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)
• Active or chronic recurrent systemic infections that require continuous antimicrobial therapy during the Kevetrin study period

Sponsors & Collaborators

• Innovation Pharmaceuticals, Inc.: lead

Study Sites (2)

Cancer Research

Lebanon, New Hampshire, 03766, United States

Location

Cancer Research

Dallas, Texas, 75230, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Cohort Studies

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Epidemiologic Studies; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Arthur P. Bertolino MD, PhD, MBA
• Organization: Innovation Pharmaceuticals

abertolino@IPharmInc.com

9789214125

Study Officials

• Arthur Bertolino, MD

  Cellceutix Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 3, 2017
• Study Start: February 9, 2017
• Primary Completion: November 10, 2017
• Study Completion: November 10, 2017
• Last Updated: December 27, 2018
• Results First Posted: December 27, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)