A Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, in Patients With Advanced Solid Tumors

NCT00842335 | Completed Phase 1 Results

• 1 other identifier: JI-101-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

solid tumors; angiogenesis inhibitor; dose escalation; maximum tolerated dose; JI-101

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of JI-101

  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.

  28 days (1 cycle)

Secondary Outcomes (3)

• Number of Participants Reaching Maximum Tolerated Dose

  Up to 112 days (up to four 28-day cycles) or longer if the patient is benefiting from treatment

• Overall Clinical Response by Cycle

  Up to 112 days ( four 28-day cycles)

• Days to Progression

  Up to 112 days (four 28-day cycles) or longer if the patient is benefiting from treatment

Study Arms (1)

JI-101

EXPERIMENTAL

Drug: JI-101

Interventions

JI-101 DRUG

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

Eligibility Criteria

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

You may qualify if:

• Be 18 years of age or greater at the time of consent.
• Have solid tumors for which no approved therapy or standard of care is available or have solid tumors and have failed standard-of-care therapy.
• Have life expectancy of greater than 3 months.
• Have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Have organ and marrow function as defined below:
• absolute neutrophil count ≥ 1.5 x 10\^9 cells/L
• hemoglobin ≥ 9.0 g/dL
• platelets ≥ 75 x 10\^9 cells/L
• total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 x ULN for liver metastases)
• serum creatinine \< 1.5 x ULN
• \< 500 mg urinary protein/24 hours or dipstick \< 2+
• No evidence of preexisting uncontrolled hypertension as documented by two baseline blood pressure readings taken at least 1 hour apart (the baseline systolic blood pressure readings must be \<140 mm Hg, and the baseline diastolic blood pressure readings must be \<90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible)
• Have no clinically significant disease that poses a risk to the patient and/or would interfere with study evaluations or procedures.
• Have within normal range cardiac function as measured by twelve-lead electrocardiogram at Screening.

You may not qualify if:

• Be pregnant or breastfeeding.
• Have a known history of human immunodeficiency virus (HIV) infection because the effect of JI-101 on immunosuppression and drug interactions with anti-retroviral medications is unknown.
• Have participated in an investigational drug/device/biologic study within 30 days (or within 5 half-lives of the treatment, whichever is longer) before Visit 1 or who are currently participating in another investigational drug/device/biologic study. Participation in non-interventional or observational studies is allowed.
• Have a history of cardiac abnormalities including: abnormal and clinically relevant ECGs; frequent palpitations or syncopal episodes; heart failure; hypokalemia; stroke; family history of Long QT Syndrome; acute myocardial infarction or ventricular tachyarrhythmia within the previous 12 months.
• Have used concomitant medications that prolong the QT/QTc interval within 14 days prior to Day 1.
• Have a history of significant retinopathy or any progressive eye disease that could lead to severe loss of visual acuity or visual field loss during the study period.
• Have had therapeutic reanticoagulation with heparin or heparin analogs (low molecular weight heparins) or warfarin within the past 4 weeks. Low dose warfarin (1 to 2 mg/day) is allowed for prophylaxis treatment.
• Have had major surgery, radiotherapy, chemotherapy, or cytokine therapy within 4 weeks of treatment initiation. Patients must have recovered to baseline or grade 1 from any clinically significant adverse event experienced during those prior therapies.
• Have gastrointestinal abnormalities including inability to take oral medications, malabsorption syndromes or other clinically significant GI abnormalities that may impair the absorption of JI-101 in the opinion of the Investigator.
• Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would pose a risk to patient safety or that would limit compliance with study requirements.
• Have any condition that, in the opinion of the Investigator, would interfere with a patient's ability to perform the required activities of the study or would subject the patient to undue risk.
• Patients with proteinuria (patients with \>2+ protein on urine dipstick) at baseline should undergo a 24-hour urine collection. Results must demonstrate \<500 mg of protein in 24 hours to allow participation in the study)
• o Inability to remain lying down in PET scanner (for PET portion of the study).
• Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose CT (computed tomography) scan or other radiographic imaging as defined by response evaluation criteria in solid tumors (RECIST) criteria.

Sponsors & Collaborators

• Jubilant Innovation Ltd.: lead

Study Sites (1)

Premiere Oncology of Arizona

Scottsdale, Arizona, 85258, United States

Location

MeSH Terms

Interventions

1-(1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl)-3-(5-bromo-2-methoxyphenyl)urea

Results Point of Contact

• Title: Jane Fisher, Senior Manager, Regulatory Affairs
• Organization: Jubilant Clinsys Inc.

jfisher@clinsys.com

+1 (919) 518-8786

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: February 11, 2009
• First Posted: February 12, 2009
• Study Start: February 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: January 1, 2012
• Last Updated: June 24, 2013
• Results First Posted: June 24, 2013

Record last verified: 2013-06

Locations

US (1)