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

Sponsor

Roswell Park Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00646139

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Lymphoproliferative Disorder Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: Src kinase inhibitor KX2-391 Other: immunoenzyme technique Other: pharmacological study	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Mar 1, 2009

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose []

Secondary Outcome Measures

Safety []
Pharmacokinetics []
Biological effects []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)