Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers
Summary
The study consists of two parts: Drug Interaction (Pharmacokinetic) Phase and Pharmacodynamic Phase
The primary study objective for the Drug Interaction Study is to determine the pharmacokinetic interactions between RAD001 and JI-101.
The primary study objective for the Pharmacodynamic Study is progression-free survival at 2 moths, evaluated separately in each of the three cohorts.
These will include a determination of tumor response using RECIST Criteria and an assessment of ephrinB4 expression in blood samples.
Secondary objectives are to determine safety and tolerability of JI-101. The investigational products are everolimus (42-O-(2-hydroxyethyl) rapamycin) and JI-101 (1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2 methoxy-phenyl)-urea)
Eligible patients meeting all study entry criteria will be enrolled in the study. For the Drug Interaction study, patients with solid tumors will receive a single dose (10 mg) of Everolimus by mouth on Day 1 and Day 8 and JI-101 capsules (200 mg) by mouth on Day 8 and Day 15. For the Pharmacodynamic Study, all patients will receive JI-101 capsules by mouth (200 mg BID) for 28 day treatment cycles.
Description
This is a multi-center, non-randomized, open-label study to evaluate the safety and efficacy of RAD001 and JI-101 in patients with solid tumors.
Patients will complete all Screening evaluations within 21 days of Study Cycle 1Day 1. All patients will provide written Informed consent and HIPAA authorization before any procedures or assessments are initiated for the purposes of the protocol.
For the Drug Interaction Study, Everolimus will be administered to eligible patients at Cycle 1 Day 1 and blood will be drawn for pharmacokinetic analyses prior to dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing. On Day 8, Everolimus and JI-101 will be administered and blood will be drawn for pharmacokinetic analyses prior to dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing. On Day 15, JI-101 will be administered and blood will be drawn for pharmacokinetic analyses prior to dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing. Patients will continue to receive JI-101(200 mg BID) for 28 day treatment cycles. Patients in the Drug Interaction Study will also receive CT scans prior to screening and every 2 treatment cycles.
For the Pharmacodynamic Study, JI-101 will be dispensed to eligible patients at Cycle 1 Day 1. JI-101 will be administered (200 mg BID) for 28 day treatment cycles. PET and CT scans will be performed prior to commencing treatment if it is standard of care. A CT scan will be performed otherwise. Patients will return to the study site every 2 cycles to complete safety assessments with radiologic tumor assessments (CT and/or PET). Adverse events will be monitored following the first administration of investigational product for the duration of the patient's participation in this study. Archival tissue will be collected for detection of mutations in relevant pathways and development of assays to study modulation of pathways that are targeted by JI-101.
Study Design
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Cancer
Intervention
JI-101, Everolimus
Location
Huntsman Cancer Institute
Salt Lake City
Utah
United States
84112
Status
Not yet recruiting
Source
University of Utah
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01149434
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:12:43-0400
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Medical and Biotech [MESH] Definitions
Everolimus
A derivative of sirolimus and an inhibitor of TOR SERINE-THREONINE KINASES. It is used to prevent GRAFT REJECTION in heart and kidney transplant patients by blocking cell proliferation signals. It is also an ANTINEOPLASTIC AGENT.
Seer Program
A cancer registry mandated under the National Cancer Act of 1971 to operate and maintain a population-based cancer reporting system, reporting periodically estimates of cancer incidence and mortality in the United States. The Surveillance, Epidemiology, and End Results (SEER) Program is a continuing project of the National Cancer Institute of the National Institutes of Health. Among its goals, in addition to assembling and reporting cancer statistics, are the monitoring of annual cancer incident trends and the promoting of studies designed to identify factors amenable to cancer control interventions. (From National Cancer Institute, NIH Publication No. 91-3074, October 1990)
Capecitabine
A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.
Gastric Stump
That portion of the stomach remaining after gastric surgery, usually gastrectomy or gastroenterostomy for cancer of the stomach or peptic ulcer. It is a common site of cancer referred to as stump cancer or carcinoma of the gastric stump.
American Cancer Society
A voluntary organization concerned with the prevention and treatment of cancer through education and research.
