A Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin in Patients With Advanced Solid Tumors
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.
Description
Kevetrin was found to be effective in pre-clinical studies of human xenograft tumor models and was reasonably well-tolerated at therapeutic doses in the non-clinical animal studies. Kevetrin was also effective in multi-drug resistant tumor models; therefore, Kevetrin has the potential to treat tumors that have become resistant to standard chemotherapy. This trial will determine tolerance in humans and, possibly, efficacy with a Phase I, open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of Kevetrin, in adult patients with solid tumors.
The primary objectives are the following:
- To determine the maximum tolerated dose (MTD) of Kevetrin.
- To determine the dose limiting toxicities (DLT) of Kevetrin.
- To establish a safe dose level of Kevetrin that can be used for future studies.
The secondary objectives are to determine the following:
- The pharmacokinetics of Kevetrin in humans.
- Observe for evidence of antitumor activity following administration of Kevetrin.
- If Kevetrin induces changes in the biomarker p21 in peripheral blood lymphocytes.
- If there is a pharmacodynamic relationship between the plasma concentrations of Kevetrin and a clinical or cellular effect.
During each 4 week cycle, each patient will receive three weekly doses of Kevetrin given as a 1 hour intravenous infusion followed by a 1 week off-treatment period. Following each dose, each patient will be monitored. If the patients have acceptable safety and tolerance, Kevetrin will be given once weekly for a total of 3 weeks. During each cycle patients will be evaluated for safety, tolerance, and Dose-Limiting Toxicity (DLT) that occur during a cycle.
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Solid Tumors
Intervention
thioureidobutyronitrile
Location
Dana-Farber / BIDMC / Harvard Cancer Center
Boston
Massachusetts
United States
02215
Status
Recruiting
Source
Cellceutix Pharmaceuticals
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01664000
- Information obtained from ClinicalTrials.gov on December 05, 2012
Medical and Biotech [MESH] Definitions
Lomustine
An alkylating agent of value against both hematologic malignancies and solid tumors.
Brenner Tumor
A smooth, solid or cystic fibroepithelial (FIBROEPITHELIAL NEOPLASMS) tumor, usually found in the OVARIES but can also be found in the adnexal region and the KIDNEYS. It consists of a fibrous stroma with nests of epithelial cells that sometimes resemble the transitional cells lining the urinary bladder. Brenner tumors generally are benign and asymptomatic. Malignant Brenner tumors have been reported.
Bleomycin
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
Mitomycins
A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.
Chromomycins
A complex of several closely related glycosidic antibiotics from Streptomyces griseus. The major component, CHROMOMYCIN A3, is used as a fluorescent stain of DNA where it attaches and inhibits RNA synthesis. It is also used as an antineoplastic agent, especially for solid tumors.
Clinical Trials
A Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, in Patients With Advanced Solid Tumors
The purpose of this study, the first clinical trial of JI-101, is to determine the maximum tolerated dose of JI-101 when given orally to patients with solid tumors. Safety, tolerability,...
Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors
The purpose of this study is to test the safety and effectiveness of 2 drugs, perifosine in combination with temsirolimus in children with solid tumors. Neither drug is currently part of t...
The purpose of this study is to determine if CVX-241 (PF-05057459) is safe and tolerable when given as weekly infusions to adult patients with advanced solid tumors.
A Phase 1 Study of ARQ 197 in Adult Patients With Advanced Solid Tumors
This is an open label, single arm, dose escalation study of ARQ 197 in patients with advanced solid tumors.
This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the...
PubMed Articles
Bioimaging and therapeutic agents accumulated in ectopic tumors following intravenous administration of hybrid nanocrystals to tumor-bearing mice. Solid, nanosized paclitaxel crystals physically incor...
Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next-generation sequencing now allows...
CT and MR features of struma ovarii.
OBJECTIVE: The purpose of this study is to investigate radiologic findings of struma ovarii, and to correlate both CT and MR findings. MAT...
Incidence of anemia, leukocytosis, and thrombocytosis in patients with solid tumors in China.
Despite the fact that malignancies are associated with hematological abnormalities, some clinical studies have been unable to detect such a relation. The aim of our study was to detect the prevalence...
Rare solid tumors of the pancreas as differential diagnosis of pancreatic adenocarcinoma.
Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer.
