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Dasatinib in Treating Patients With Metastatic or Unresectable Solid Tumor or Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), January 2009
First Received: January 30, 2008   Last Updated: February 24, 2009   History of Changes
Sponsors and Collaborators: Southwest Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00608361
  Purpose

RATIONALE: Dasatinib may stop the growth of tumor 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 dasatinib in treating patients with metastatic or unresectable solid tumor or lymphoma.


Condition Intervention Phase
Liver Cancer
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: dasatinib
Other: pharmacological study
Phase I

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Liver Cancer Lymphoma
Drug Information available for: Dasatinib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517; IND-73969) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: October 2008
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To estimate the maximum tolerated dose of dasatinib in patients with varying degrees of hepatic impairment.
  • To estimate the pharmacokinetic (PK) profile of this drug in these patients.
  • To assess the safety profile and dose-limiting toxicities (if any) of this drug in these patients.

Secondary

  • To describe any antitumor efficacy associated with this drug in these patients.
  • To examine whether the PK clearance of dasatinib correlates with hepatic function as assessed by Child-Pugh Criteria, the NCI Organ Dysfunction Working Group Criteria, or other assessments of liver function such as total bilirubin level.

OUTLINE: This is a multicenter study. Patients are stratified according to hepatic function as defined by the Child-Pugh classification system (control [i.e., total bilirubin normal, AST/ALT normal, and PT normal, and Child-Pugh classification score of 5] vs mild impairment [Child-Pugh class A] vs moderate impairment [Child-Pugh class B] vs severe impairment [Child-Pugh class C]).

Patients receive oral dasatinib once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating dose of dasatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Patients undergo blood sample collection on days 1 and 8 of course 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically for 28 days.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed solid tumor or lymphoma

    • Metastatic or unresectable disease
    • Standard curative or palliative measures do not exist or are no longer effective
    • All solid and lymphoma tumor types are eligible
    • Patients with a liver mass, elevated α-fetoprotein level (i.e., ≥ 500 ng/mL), and positive serology for viral hepatitis consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of diagnosis
  • Measurable or nonmeasurable disease
  • Patients with brain metastases requiring corticosteroids must be on a stable or decreasing dose of corticosteroids

    • Prior brain irradiation (whole brain or gamma knife) is required for known brain metastases
    • No untreated (non-irradiated) brain metastases
  • No baseline pleural effusion or ascites

    • Patients with a history of pleurodesis and previous pleural effusion (malignant or non-malignant) may be eligible but treated with caution
    • Patients with ascites may be treated

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • Life expectancy ≥ 2 months
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Magnesium ≥ lower limit of normal (LLN)
  • Potassium ≥ LLN
  • Creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
  • Patients with abnormal liver function are eligible
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with biliary obstruction for which a shunt has been placed are eligible provided the liver function tests have stabilized

    • Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function
    • There must be no evidence of biliary sepsis and at least 2 weeks must have elapsed after the placement of a biliary shunt
  • Must be willing to undergo pharmacokinetic sampling
  • Must be able to take oral medications
  • None of the following within the past 12 months:

    • Myocardial infarction
    • Severe/unstable angina
    • Coronary/peripheral artery bypass graft
    • Congestive heart failure
    • Cerebrovascular accident including transient ischemic attack
    • Significant pulmonary embolus
  • No history of allergic reaction to dasatinib or similar compounds
  • No ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 470 msec for females or > 450 msec for males
  • No active gastrointestinal bleeding
  • No diagnosis of malabsorption syndrome or significant bowel resection affecting absorption
  • No clinically significant fluid retention or pericardial effusion
  • No uncontrolled serious intercurrent medical illness including, but not limited to, any of the following:

    • Ongoing or serious active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • Uncontrolled diarrhea
    • Psychiatric illness/social situation that would limit compliance with study requirements
  • No known HIV-positivity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered form all prior therapy
  • More than 7 days since prior and no concurrent H2-receptor antagonist (e.g., cimetidine, ranitidine, or famotidine)
  • More than 7 days since prior and no concurrent proton pump inhibitors (e.g., omeprazole, lansoprazole, esomeprazole, or pantoprazole)
  • More than 4 weeks since prior major surgical procedures
  • More than 4 weeks since prior and no other concurrent or plans to receive anticancer therapy including chemotherapy, radiotherapy, immunotherapy, or investigational agents
  • At least 2 weeks since prior targeted agents with a half-life of < 24 hours
  • No prior dasatinib
  • Concurrent hormone therapy for prostate carcinoma may be continued
  • Concurrent bisphosphonate treatment for bone disease is permitted
  • No concurrent therapeutic doses of anticoagulants

    • Low dose warfarin for port prophylaxis is permitted
  • No concurrent enzyme-inducing anticonvulsant medications (e.g., phenobarbital, phenytoin, or carbamazepine)
  • No concurrent prophylactic colony-stimulating factors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00608361

Locations
United States, Texas
Cancer Therapy and Research Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Clinical Trials Office - Cancer Therapy and Research Center     210-616-5798        
University Hospital - San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: John Sarantopoulos     210-358-4000        
University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229-3900
Contact: John Sarantopoulos     210-567-4777        
Veterans Affairs Medical Center - San Antonio (Murphy) Recruiting
San Antonio, Texas, United States, 78209
Contact: John Sarantopoulos     210-617-5300        
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: John Sarantopoulos, MD Cancer Therapy and Research Center, Texas
Investigator: Chris H. Takimoto, MD, PhD, FACP South Texas Accelerated Research Therapeutics
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000583976, SWOG-S0711
Study First Received: January 30, 2008
Last Updated: February 24, 2009
ClinicalTrials.gov Identifier: NCT00608361     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
Waldenstrom macroglobulinemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma

Study placed in the following topic categories:
Liver Diseases
Carcinoma, Hepatocellular
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Protein Kinase Inhibitors
Ileal Diseases
Follicular Lymphoma
Duodenal Neoplasms
Mycoses
Leukemia, Lymphocytic, Chronic, B-Cell
Dasatinib
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Digestive System Neoplasms
Immunoproliferative Disorders
Carcinoma
Waldenstrom Macroglobulinemia
B-cell Lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Gastrointestinal Diseases
Lymphoma, Follicular
Central Nervous System Lymphoma, Primary
Lymphoma, B-Cell, Marginal Zone
Sezary Syndrome
Mycosis Fungoides
Lymphoblastic Lymphoma

Additional relevant MeSH terms:
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Ileal Diseases
Protein Kinase Inhibitors
Duodenal Neoplasms
Liver Neoplasms
Neoplasms by Site
Ileal Neoplasms
Jejunal Diseases
Dasatinib
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Neoplasms by Histologic Type
Digestive System Neoplasms
Immunoproliferative Disorders
Immune System Diseases
Enzyme Inhibitors
Intestinal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Lymphatic Diseases
Neoplasms
Digestive System Diseases
Gastrointestinal Neoplasms
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on May 07, 2009