A Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin in Patients With Advanced Solid Tumors

NCT01664000 | Completed Phase 1 DMC

• 2 other identifiers: CTIX 12-10112-151
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

In the laboratory, Kevetrin activates p53, a tumor suppressor protein that has an important role in protecting the body. p53 functions by activating proteins that repair DNA and kill cells that have genetic mutations such as in cancers. Research experiments showed that when cancer cells were treated with Kevetrin, it activated p53 which induced p21, a protein that inhibits cancer cell growth. p53 also induced PUMA (p53 up-regulated modulator of apoptosis), a protein that causes tumor cell death. Because of these activities, slowing cancer cell growth and causing cancer cell death, Kevetrin may help to treat tumors.

Conditions

Solid Tumors

Keywords

Tumors; carcinoma; apoptosis; p53; p21; Caspase3; PARP; MDM2; PUMA

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Kevetrin

  A dose will be declared the MTD if at least 1 patient out of 6 patients experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. Once an MTD has been established, up to 12 additional patients may be enrolled at the MTD dose level for confirmation of safety. The maximally administered dose is if 1 or more of 6 patients experience a DLT.

  up to 6 months

• Dose Limiting Toxicities (DLT) of Kevetrin.

  The definition of dose limiting toxicity (DLT) is in accord with the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Dose limiting toxicity will be defined as: * Grade 3 or 4 neutropenia complicated by fever, or greater than 38.5°C documented infection, or Grade 4 neutropenia of greater than 7 days duration * Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated by hemorrhage * Any grade greater than 3 non-hematologic toxicity unless there is clear alternative evidence that the adverse event (AE) was not caused by Kevetrin * Grade 3 diarrhea, nausea, or vomiting may be excluded from dose-limiting toxicities provided that the maximum time limit for supportive measures is 48 hours.

  up to 4 weeks

Secondary Outcomes (13)

• Pharmacokinetic Profile of Kevetrin

  Day 1 Pre-dose, 30 minutes after starting the infusion, 1 hr, 1 hr 10 min, 1 hr 20 min, 1 hr 30 min, 1 hr 45 min, 2 hr, 2 hr 30 min, 3 hr, 4 hr, 5 hr, 7 hr, and 24 hr after the initiation of the infusion

• Pharmacokinetic Profile of Kevetrin

  Day 15 Pre-dose, 30 minutes after starting the infusion, 1 hr, 1 hr 10 min, 1 hr 20 min, 1 hr 30 min, 1 hr 45 min, 2 hr, 2 hr 30 min, 3 hr, 4 hr, 5 hr, 7 hr, and 24 hr after the initiation of the infusion

• Change in tumor size

  baseline and 2 months

• Change in tumor size

  baseline and 4 months

• Change in tumor size

  baseline and 6 months

Study Arms (1)

Kevetrin

EXPERIMENTAL

thioureidobutyronitrile intravenous once/week for 3 weeks/ cycle

Drug: thioureidobutyronitrile

Interventions

thioureidobutyronitrile DRUG

Kevetrin (thioureidobutyronitrile)

Also known as: Kevetrin

Kevetrin

Eligibility Criteria

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

You may qualify if:

• Males / females, ≥ 18 years old, any race / ethnicity, who can provide written Informed Consent
• Life expectancy ≥ 3 months
• Pathologically confirmed solid tumor, locally advanced / metastatic, refractory after standard therapy, or for which no effective curative or surgical treatment options are available
• Measurable disease on baseline imaging per RECIST 1.1 criteria
• ECOG performance status ≤ 1
• Liver function:
• Bilirubin ≤ 1.5 X upper limit of normal
• AST, SGOT, ALT, SGPT ≤ 2.5 X upper limit of normal, \< 5 upper limit if there are liver metastases
• Renal function:
• Serum creatinine within normal limits
• Hematologic status:
• Absolute neutrophil count ≥ 1500 cells/mm3.
• Platelet count ≥ 100,000/mm3.
• Hemoglobin ≥ 9 g/dL
• Coagulation status:

You may not qualify if:

• History of significant disease that in the Investigator's opinion would put the patient at high risk on the trial
• Cognitive impairment sufficient to render the patient incapable of giving informed consent
• History of clinically significant psychiatric illness that would prevent the patient from providing a valid ICF and complying with protocol requirements
• Unwillingness or inability to comply with procedures required in this protocol
• History or presence of alcoholism or drug abuse within the past 2 years
• Patients who have had a major surgical procedure within the past 6 weeks
• History of HIV, hepatitis B, or hepatitis C
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
• Women of childbearing potential who are lactating, pregnant or there is the likelihood of becoming pregnant within the coming 12 months; a positive serum beta-human chorionic gonadotropin test at time of screening for entry into study
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
• Patients with a mean QTc interval greater than 480ms are excluded. Avoid concomitant administration of agents that prolong the QT interval, except at the discretion of the investigator. If advised, patients should discontinue the use of these agents at least 2 weeks before the study begins. No uncontrolled arrhythmias.
• Patients currently receiving other investigational agents
• Participation in a study of an investigational drug within 4 weeks prior to the planned first day of study drug administration
• Patients who have undergone radiation within the past 4 weeks
• Treatment with molecularly targeted agents within the past 3 weeks prior to planned first study drug administration. Patients who were receiving standard chemotherapy or experimental therapies must wait 4 weeks from their last dose prior to the planned first study drug administration. Patients treated with nitrosoureas or mitomycin C must wait 6 weeks from their last dose prior to the planned first study drug administration.

Sponsors & Collaborators

• Cellceutix Corporation: lead
• Dana-Farber Cancer Institute: collaborator
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

Dana-Farber / Beth Israel Deaconess Medical Center / Harvard Cancer Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma; Spinocerebellar Ataxias

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Geoffrey Shapiro, MD PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: August 14, 2012
• Study Start: October 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 24, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)