Safety Study to Evaluate KW-2450 in Subjects With Advanced Solid Tumor

NCT00921336 | Completed Phase 1

• 1 other identifier: 2450-US-001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

This study will determine the maximum dose of KW-2450 that can be administered safely to subjects with advanced previously treated solid tumor and evaluate its effectiveness.

Conditions

Solid Tumor

Keywords

subjects with advanced Solid tumor who have not responded to standard therapy or for whom no standard therapy is available

Outcome Measures

Primary Outcomes (1)

• To establish the safety, tolerability, and recommended Phase 2 dose of KW 2450 administered orally in subjects with advanced solid tumor who have not responded to standard therapy or for whom no standard therapy is available

  28 days

Secondary Outcomes (2)

• To determine the PK/PD profile of KW-2450

  PK/PD perfomed up to Day 29 Tumor assessments performed at 8 weeks

• To evaluate for preliminary evidence of efficacy

  PK/PD perfomed up to Day 29 Tumor assessments performed at 8 weeks

Study Arms (1)

KW-2450

EXPERIMENTAL

Drug: KW-2450

Interventions

KW-2450 DRUG

Dose escalation may proceed once \>= 3 subjects have completed the Day 29 blood sample to evaluate glucose. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially with accelerated escalation. Once the criteria for completing the accelerated titration are reached, dose escalation will follow a modified Fibonacci schedule. Up to 6 subjects will be enrolled at each dose level. Enrollment will proceed until the maximum tolerated dose (MTD) has been established or the highest dose level (800 mg/day) has been reached. The Sponsor will enroll up to 12 additional subjects, in an expanded safety cohort.

KW-2450

Eligibility Criteria

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

You may qualify if:

• Voluntary signed and dated Institutional Review Board (IRB) approved informed consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with regulatory and institutional guidelines. This must be obtained before performing protocol-related procedures that are not part of standard subject care
• Histopathologically- or cytologically-documented, advanced primary or recurrent solid tumor that has not responded to an adequate course of available therapy, that has progressed or recurred despite an adequate course of available therapy, that is not curable by available therapy or for which no accepted standard therapy exists
• Ability to comply with visits/procedures required by the protocol. Subjects enrolled in this trial must be treated at a participating center
• A life expectancy of \>3 months
• Eastern Cooperative Oncology Group (ECOG) performance status score of \<= 2 at study entry
• Adequate hematologic function, as defined by:
• an absolute neutrophil count (ANC) \>= 1500/mm3 a hemoglobin level \>=8.5 gm/dL a platelet count \>=100,000/mm3
• Adequate hepatic function, as defined by:
• a total bilirubin level \<= 1.5 x the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine transaminase (ALT) levels \<= 2.5 x the ULN or \<= 5 x the ULN if known liver metastases
• Adequate renal function, as defined by:
• a serum creatinine (Scr) \<= 1.5 mg/dL for male subjects; Scr \<= 1.40 mg/dL for female subjects Calculated creatine clearance \> 60 mL/min based on Cockcroft-Gault formula
• Subjects must be recovered from the effects of any prior anti-neoplastic therapy. The ongoing adverse events due to these therapies must be \<=Grade 1 prior to entering the study. At least 5 half-lives should have elapsed for any investigational agents prior to the administration of study medication
• Subjects with central nervous system (CNS) metastases are eligible for enrollment if they have received prior radiotherapy and/or surgery to site(s) of CNS metastatic disease, have been off glucocorticoids for at least 4 weeks, are not taking anticonvulsants, and have no overt evidence of neurological deficit
• Men and women, \>= 18 years of age at the time of enrollment
• Women of childbearing potential (WOCBP) must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm) or abstain from sexual intercourse during the study and for 90 days following the last dose of KW-2450.

You may not qualify if:

• Women who are pregnant or lactating
• Known diabetes defined as:
• random serum glucose concentration of \> 200 mg/dL
• fasting plasma glucose (FPG) of \> 126 mg/dL
• hour post load serum glucose concentration of \> 200 mg/dL following an oral glucose tolerance test
• the need for an oral hypoglycemic agent or insulin in order to keep the serum glucose below the above levels; or
• any diabetic complication (cataract, retinopathy, nephropathy, etc.).
• Subjects showing clinical evidence or with a history of cataract(s) or retinopathy
• Abnormal free T4 values. Abnormal thyroid stimulating hormone (TSH) values at enrollment will be further evaluated by free T4. Subjects with abnormal free T4 values and a history or evidence of thyroid disease will be excluded.
• Subjects who are unable or unwilling to take metformin
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring parenteral antibiotics;
• A serious or nonhealing active wound, ulcer, or bone fracture;
• Uncontrolled hypertension (systolic blood pressure \>160 mm Hg, diastolic blood pressure \>100 mm Hg, found on two consecutive measurements separated by a 1week period despite treatment with two antihypertensive agents)
• Unstable cardiovascular disease (i.e., including uncontrolled ischemic heart disease, congestive heart failure, arrhythmia or hypertension; New York Heart Association \>= class III; or myocardial infarction or acute coronary syndrome within 6 months)

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Study Sites (3)

University of Maryland Greenbaum Cancer Center

Baltimore, Maryland, 21201-1595, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering

New York, New York, 10021, United States

Location

MeSH Terms

Interventions

KW-2450

Study Officials

• Michael Kurman, MD

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

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: May 27, 2009
• First Posted: June 16, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (3)