KX2-391 in Treating Patients With Advanced Solid Tumors or Lymphoma That Did Not Respond to Treatment

March 1, 2011 updated by: Roswell Park Cancer Institute

A Combined Rising Single-Dose (RSD) and Rising Multiple-Dose (RMD) Phase 1 Study to Evaluate Safety, Tolerability and Pharmacokinetics of KX2-391 in Patients With Advanced Malignancies That Are Refractory to Conventional Therapies

RATIONALE: KX2-391 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of KX2-391 in treating patients with advanced solid tumors or lymphoma that did not respond to treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

To define the maximum tolerated dose of KX2-391 when administered as multiple oral solutions in patients with refractory advanced solid tumors and lymphoma.

Secondary

To determine the safety and tolerability of KX2-391 given as single and multiple oral solutions in these patients.
To characterize the pharmacokinetic profile of single dosing and multiple dosing of KX2-391 in these patients.
To determine the biological effects of KX2-391.

OUTLINE: This is a multicenter study.

Patients receive oral KX2-391 once or twice daily for 3 weeks. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected periodically for pharmacokinetic studies. Biological effects are assessed by measuring plasma levels of vascular endothelial growth factor by ELISA. Levels of phospho-Src Tyr and transphosphorylation of selected substrates are measured in peripheral blood mononuclear cells.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- New York
  - Buffalo, New York, United States, 14263-0001
    - Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Confirmed diagnosis of advanced solid tumor or lymphoma
- Metastatic or unresectable disease
- Standard curative or palliative measures do not exist or are no longer effective
Patients with treated brain or ocular metastases are eligible

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 14 weeks
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10 g/dL
Serum bilirubin ≤ 2.5 times upper limit of normal (ULN)
ALT and AST ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Serum creatinine ≤ 1.5 times ULN or creatinine clearance > 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception for 1 month prior to, during, and for 6 months after completion of study treatment
No inflammatory bowel disease, malabsorption syndrome, or other medical condition that may interfere with oral drug absorption
No signs or symptoms of end organ failure, major chronic illnesses other than cancer, or any severe concomitant conditions including, but not limited to, active infections that, in the opinion of the investigator, precludes protocol participation or compliance
No history of any of the following within the past 6 months:
- Angina pectoris
- Coronary artery disease
- Hypertension
- Cerebral vascular accident
- Transient ischemic attack uncontrolled by medical therapy
No history of confirmed cardiac conduction abnormalities or arrhythmias
No known history of hepatitis B or C, or HIV infection
No known history of coagulation disorders or hemolytic conditions (e.g., sickle cell anemia)

PRIOR CONCURRENT THERAPY:

Recovered from all prior therapy
No prior major surgery to the upper gastrointestinal tract
More than 2 weeks since prior investigational agents or systemic anticancer agents (28 days for agents with unknown elimination half-lives or known elimination half-lives > 50 hours)
More than 4 weeks since prior radiotherapy to the sternum, pelvis, scapulae, vertebrae, or skull and recovered
More than 4 weeks since prior major surgery
More than 1 week since prior palliative low-dose radiotherapy to the limbs and recovered
More than 2 weeks since prior and no concurrent hormones (e.g., estrogen contraceptives, hormone replacement, anti-estrogen, or progesterone) or antiplatelet agents
More than 2 weeks since prior and no concurrent anticoagulants (e.g., coumadin) except prophylactic doses of anticoagulants for indwelling venous catheters
More than 2 weeks or 5 half-lives since prior and no concurrent cytochrome P450 modulators (e.g., strong inducers or inhibitors)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose

Secondary Outcome Measures

Outcome Measure
Safety
Pharmacokinetics
Biological effects

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Investigators

Principal Investigator: Alex A. Adjei, MD, PhD, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

March 27, 2008

First Submitted That Met QC Criteria

March 27, 2008

First Posted (Estimate)

March 28, 2008

Study Record Updates

Last Update Posted (Estimate)

March 2, 2011

Last Update Submitted That Met QC Criteria

March 1, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000589972
RPCI-I-112607
KINEX-KX01-01-07

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.