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

This study has been completed.
Sponsor:
Information provided by:
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00646139
First received: March 27, 2008
Last updated: March 1, 2011
Last verified: March 2011
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]
  • Biological effects [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: October 2007
Study Completion Date: March 2009
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00646139

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Alex A. Adjei, MD, PhD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alex Adjei, MD, Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00646139     History of Changes
Other Study ID Numbers: CDR0000589972, RPCI-I-112607, KINEX-KX01-01-07
Study First Received: March 27, 2008
Last Updated: March 1, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
unspecified adult solid tumor, protocol specific
recurrent adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoproliferative Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 21, 2014