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

Status: Recruiting
Phase: Phase 1
Diagnosis: Solid Tumor/Phase I
NCT ID: NCT01664000 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-151

 

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.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Beth-Israel Deaconess Medical Center, Brigham and Women's Hospital

Overall PI:
Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Daniel Cho, MD, Beth Israel Deaconess Medical Center

Contacts:
Dana-Farber Cancer Institute: Andrew Wolanski, 617-632-6623, andrew_wolanski@dfci.harvard.edu
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

Inclusion Criteria: - Males or females, greater than or equal to 18 years of age, of any race or ethnicity, who can provide written Informed Consent. - Patients with a life expectancy of at least 3 months. - Pathologically confirmed solid tumor which is locally advanced or metastatic, and either refractory after standard therapy for the disease, or for which no effective curative or surgical treatment options are available - Must have evaluable or measurable disease on baseline imaging (e.g., CT scan, PET, MRI) per RECIST 1.1 criteria to meet eligibility. - ECOG performance status less than or equal to 1 - Acceptable liver function: - Bilirubin less than or equal to 1.5 times the upper limit of normal - AST (SGOT), ALT (SGPT)less than or equal to 2.5 times the upper limit of normal, less than 5 times the upper limit if there are liver metastases. - Acceptable renal function: - Serum creatinine within normal limits, or calculated creatinine clearance greater than or equal to 60 mL/min/1.73m2 by the Cockcroft and Gault equation or 24 hour urine creatinine clearance. - Acceptable hematologic status: - ANC greater than or equal to 1500 cells/mm3. For patients to be eligible for a new treatment cycle, ANC must be greater than or equal to 1000 cells/mm3 - Platelet count greater than or equal to 100,000/mm3. For patients to be eligible for a new treatment cycle, platelet count must be greater than or equal to 75,000 /mm3. - Hemoglobin greater than or equal to 9 g/dL - Acceptable coagulation status: - PT less than or equal to 1.5 times the upper limit - PTT less than or equal to 1.5 times the upper limit - All males in the study must agree to always use condoms during sex to prevent spillage of semen for the duration of the study and for 3 months after the patient leaves the study. - If the patient is female, she must not be pregnant or breast feeding and not planning to become pregnant or breast feed for the duration of the study, and for at least three months after study completion. - All women of childbearing potential must commit to using a double barrier method of contraception (e.g., diaphragm and condom), an intrauterine device (IUD), or sexual abstinence for the duration of the study and for at least three months after study completion. - A serum pregnancy test for women of child bearing potential must be negative at entry into study. - Written voluntary informed consent: the patient is capable of complying with the requirements of the written ICF and complying with protocol requirements. Exclusion Criteria: - History of clinically significant psychiatric illness that would prevent the patient from providing a valid ICF and complying with protocol requirements. - History of significant disease that in the Investigator's opinion would put the patient at high risk on the trial. - 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. - Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. - 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. - Patients who have undergone radiation within the past 4 weeks. - Patients with known brain metastases may be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients may be eligible if scans show limited disease or repeat scans show stable disease in the opinion of the investigator and patients have no ill effect from the metastases. - Patients who have had a major surgical procedure within the past 6 weeks. - Unwillingness or inability to comply with procedures required in this protocol. - History of HIV, hepatitis B, or hepatitis C. - History or presence of alcoholism or drug abuse within the past 2 years. Participation in a study of an investigational drug within 4 weeks prior to the planned first day of study drug administration. - Patients who are currently receiving any other investigational agents. Cognitive impairment sufficient to render the patient incapable of giving informed consent. - 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-hCG test at time of screening for entry into study. - Herbal supplements, e.g., Saint John's Wort, Milk Thistle, are prohibited 1 week prior to the planned first study drug administration, during the clinical study, and up to the time that the patient is discharged from the study. Use of Senekot is permitted. - Patients who have been exposed to medications, herbal preparations, or foods known to be predominant CYP450 2C9, 2C19, 2D6, 3A4/5 substrates, strong inhibitors or inducers within 7 days of planned first study treatment day - Patients who in the opinion of the Investigator would not be able to provide reliable study data or be available for study follow-up.
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