Clinical trial NCT00646139: KX2-391 in Treating Patients With Advanced Solid Tumors or Lymphoma That Did Not Respond to 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Lymphoproliferative Disorder
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
stage IV mycosis fungoides/Sezary syndrome
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
intraocular lymphoma
primary central nervous system non-Hodgkin lymphoma
post-transplant lymphoproliferative disorder
cutaneous B-cell non-Hodgkin lymphoma
Waldenstrom macroglobulinemia
small intestine lymphoma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2008-03-28
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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)

Primary outcomes:
measure: Maximum tolerated dose
Secondary outcomes:
measure: Safety
measure: Pharmacokinetics
measure: Biological effects
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Alex A. Adjei, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: