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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00646139
• Other study ID #: CDR0000589972
• Secondary ID: RPCI-I-112607KIN
• Status: Completed
• Phase: Phase 1
• First received: March 27, 2008
• Last updated: March 1, 2011
• Start date: October 2007
• Est. completion date: March 2009

Study information

• Verified date: March 2011
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: March 2009
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Small Intestine Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• Src kinase inhibitor KX2-391

Other:
• immunoenzyme technique

• pharmacological study

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose			Yes
Secondary	Safety			Yes
Secondary	Pharmacokinetics			No
Secondary	Biological effects			No