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, pharmacokinetics, pharmacodynamics, and the effects of the drug on tumor metabolism will also be studied. JI-101 is an inhibitor of new blood vessel growth that may provide benefit to patients with solid tumors that have failed standard therapeutic regimens.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors|
- Maximum Tolerated Dose (MTD) of JI-101 [ Time Frame: 28 days (1 cycle) ] [ Designated as safety issue: Yes ]
The primary objective of this study was to determine the maximum tolerated dose (MTD) of JI-101 when administered orally in patients with advanced solid tumors.
The MTD was established based on safety data from Cycle 1. Patients who completed 21 days of treatment in Cycle 1 were considered to have completed the study for the determination of MTD.
Patients were eligible to continue treatment with JI-101 until they experienced disease progression or unacceptable treatment-related toxicity. Unacceptable treatment-related toxicity was defined as a clinically significant AE or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, and that was attributed to JI 101.
- Number of Participants Reaching Maximum Tolerated Dose [ Time Frame: Up to 112 days (up to four 28-day cycles) or longer if the patient is benefiting from treatment ] [ Designated as safety issue: Yes ]Number of participants withdrawn from study due to adverse events
- Overall Clinical Response by Cycle [ Time Frame: Up to 112 days ( four 28-day cycles) ] [ Designated as safety issue: No ]
Stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions
- Days to Progression [ Time Frame: Up to 112 days (four 28-day cycles) or longer if the patient is benefiting from treatment ] [ Designated as safety issue: No ]Progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions
|Study Start Date:||February 2009|
|Study Completion Date:||January 2012|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
JI-101, 50 mg capsules, will be administered daily for up to 112 days (four 28-day cycles); treatment may be extended if, in the opinion of the investigator, a patient has tolerated the treatment and appears to be benefitting from receiving study medication
JI-101 is a compound being developed for the treatment of patients with solid tumors; specifically patients for which no approved therapy or standard of care is available or have solid tumors and have failed standard of care therapy. JI-101 is an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRβ), and EphB4 receptor, each of which plays an important role in driving vascularization (angiogenesis and vasculogenesis) during normal development and tumorigenesis. JI-101 inhibits the growth of new blood vessels, which in turn, may slow or prevent the growth of tumors. The purpose of this open label study is to treat patients with advanced solid tumors, with increasing doses of JI-101, thereby providing information about the maximum tolerated dose (MTD). The study will also examine safety, tolerability, pharmacokinetics, pharmacodynamics, and may evaluate the effects of the drug on tumor metabolism. During this dose-escalation study, at least two patients will be dosed at each dose level (cohort). The patients must complete 21 days of dosing and safety results will be reviewed prior to any patients being assigned the next higher dose level. A continuous reassessment method will be utilized to escalate JI-101 doses between cohorts. Doses will be increased, with an anticipated high dose of 800mg per day. If the MTD is not reached, an optimal biologic dose (OBD) will be determined based on the highest doses that are tolerable with acceptable efficacy. The cohort at MTD or OBD will be expanded to include up to 30 patients with solid tumors to further explore the safety and tolerability of orally-administered JI-101.