Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00608361
First received: January 30, 2008
Last updated: July 28, 2014
Last verified: May 2014
  Purpose

This phase I trial studies the side effects and best dose of dasatinib in treating patients with solid tumors or lymphomas that are metastatic or cannot be removed by surgery. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Acute Lymphoblastic Leukemia in Remission
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Localized Resectable Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Progressive Hairy Cell Leukemia, Initial Treatment
Recurrent Adult Acute Lymphoblastic Leukemia
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 Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult Primary Liver Cancer
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone 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 Adult T-cell Leukemia/Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
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 IIIA Mycosis Fungoides/Sezary Syndrome
Stage IIIB Mycosis Fungoides/Sezary Syndrome
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 Adult T-cell Leukemia/Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
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
Stage IVA Mycosis Fungoides/Sezary Syndrome
Stage IVB Mycosis Fungoides/Sezary Syndrome
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Hairy Cell Leukemia
Waldenström Macroglobulinemia
Drug: dasatinib
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of dasatinib, defined as the highest dose level at which less than 33% of 6-9 evaluable patients experience dose-limiting toxicity [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Toxicity will be graded according to the NCI CTCAE v3.0.

  • Pharmacokinetic parameters of dasatinib [ Time Frame: Days 1 and 8 of course 1 ] [ Designated as safety issue: No ]
    Area under curve (AUC)(to infinity), AUC(to 24 hours), and maximum concentration (Cmax) analyzed in the natural log scale. For each PK parameter, the mean difference between the recommended dose for a liver impairment group and the normal liver function group dosed at 140 mg OD (equivalent to ratios of geometric means in the non-log scale) will be tested against 0 at a one-sided 0.05 significance level to detect an increase in the liver impairment group (equivalent to a 2-sided 90% confidence interval).


Other Outcome Measures:
  • Liver dysfunction data [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The Child-Pugh classification (CPC), NCI Organ Dysfunction Working Group (ODWG) Stratification Criteria for all patients will be collected at baseline and correlated to the toxicities and pharmacokinetic data seen with dasatinib in an exploratory analysis. Clearance estimates for each liver impairment group based upon the NCI ODWG Criteria, CPC Scheme, will be correlated with drug clearance. Ultimately, the predictive value of these various different methods of grouping organ dysfunction patients will be compared to determine if any method is better able to predict dasatinib clearance.


Estimated Enrollment: 42
Study Start Date: October 2008
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib)
Patients receive dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of dasatinib in patients with varying degrees of hepatic impairment.

II. To estimate the pharmacokinetic (PK) profile of this drug in patients with varying degrees of hepatic impairment.

III. To assess the safety profile and dose-limiting toxicities (if any) of dasatinib in patients with varying degrees of hepatic impairment.

SECONDARY OBJECTIVES:

I. To describe any antitumor efficacy associated with dasatinib administration in patients with varying degrees of hepatic impairment.

II. To examine whether the pharmacokinetic clearance of dasatinib correlates with hepatic function as assessed by Child-Pugh Criteria, the National Cancer Institute (NCI) Organ Dysfunction Working Group Criteria, or other assessments of liver function.

OUTLINE: This is a dose-escalation study.

Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed solid tumor or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; patients with a liver mass, elevated alpha-fetoprotein level (>= 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 the diagnosis; all solid and lymphoma tumor types are eligible
  • Patients must have measurable or non-measurable disease; x-rays and/or scans for disease assessment must have been completed within 28 days (for measurable disease) or 42 days (for non-measurable disease) prior to registration; all disease must be assessed and documented on the web-based Baseline Tumor Assessment Form
  • Patients with brain metastases who require corticosteroids must be on stable or decreasing dose of corticosteroids; patients with known brain metastases must have had brain irradiation (whole brain or gamma knife); patients with untreated (non-irradiated) brain metastases are not eligible; patients on enzyme-inducing anticonvulsant medications (e.g. phenobarbital, phenytoin or carbamazepine) are not eligible
  • Patients must not be taking H2-receptor antagonists such as cimetidine, ranitidine, and famotidine, or any proton pump inhibitors, such as omeprazole, lansoprazole, esomeprazole, and pantoprazole; patients must stop these medications within 7 days prior to starting treatment
  • Patients must not have had anticancer therapy including chemotherapy, radiotherapy, immunotherapy, or investigational agent within 4 weeks prior to registration, except for targeted agents with half-life known to be < 24 hours; patients must not have had targeted agents with half-life < 24 hours within 2 weeks prior to registration; patients also must have recovered from serious adverse events due to agents administered within these acceptable time frames
  • Patients must not be planning to receive concurrent radiation, other chemotherapy, immune therapy or any other investigational agents for malignancy while receiving protocol treatment; hormonal treatment for prostate carcinoma may be continued and bisphosphonate treatment for bone disease is permitted
  • Patient must not have received prior therapy with dasatinib (BMS-354825)
  • Patients for whom there is a strong suspicion of being allergic to dasatinib because of a history of allergic reactions to similar compounds are not eligible
  • Patients must not have had major surgical procedures within the last 4 weeks prior to the first planned dose of study drug
  • Patients must not be taking therapeutic doses of anticoagulants; low dose warfarin for port prophylaxis is permitted
  • Zubrod performance status of 0-2
  • Patients may not have any clinically significant cardiovascular disease including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within 6 months
    • Prolonged corrected QT interval (QTc) >= 480 msec (Fridericia correction)
    • Ejection fraction less than institutional normal
    • Major conduction abnormality (unless a cardiac pacemaker is present)
    • Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction should be excluded from the study
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Magnesium >= lower limit of normal (LLN)
  • Potassium >= LLN
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 60 mL/min/1.73 m^2; if less than the normal range, supplementation should be initiated in the manner deemed appropriate by the treating physician
  • Patients with abnormal liver function are eligible and will be grouped according to the criteria; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; for patient registration, liver function tests (total bilirubin, aspartate aminotransferase [AST]/alanine aminotransferase [ALT], prothrombin time [PT]/international normalized ratio [INR] and partial thromboplastin time [PTT], and alkaline phosphatase) must be performed within 14 days prior to registration; for patient stratification, liver function tests must be performed within 72 hours of anticipated starting time of protocol treatment; patients must be stratified and treated based on the liver function tests performed within 72 hours prior to treatment; the South West Oncology Group (SWOG) Data Operations Center must be notified in writing in cases where the patient's cycle 1 pre-treatment liver function tests result in stratification to a dysfunction group different from how the patient was classified at registration
  • Patients with biliary obstruction for which a shunt has been placed are eligible, provided the liver function tests have stabilized (two measurements at least two 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
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; since interaction with dasatinib and oral contraceptives is possible, a barrier method should be used and oral contraceptives are not permitted; a negative pregnancy test is required within 72 hours prior to starting therapy for women of reproductive potential; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients who have experienced any of the following within the 12 months prior to starting protocol treatment are not eligible: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or significant pulmonary embolus
  • Patients with ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2, atrial fibrillation of any grade, or QTc interval > 470 msec for females or > 450 msec for males are not eligible
  • Patients with baseline pleural effusion are not eligible
  • Patients must not have active gastrointestinal bleeding
  • Patients with the inability to take oral medications, with a diagnosis of malabsorption syndromes or with significant bowel resection affecting absorption are not eligible
  • Patients with a clinically significant pleural effusion/ fluid retention/pericardial effusion are not eligible; patients with a history of pleurodesis and previous pleural effusion (malignant or non-malignant) may be eligible but treated with caution; patients with previous history of ascites may be treated
  • Patients with uncontrolled serious intercurrent medical illness including, but not limited to ongoing or serious active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, uncontrolled diarrhea or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
  • Patients known to be human immunodeficiency virus (HIV)-positive are not eligible; however, patients will not routinely be screened for HIV
  • Patients must be willing to undergo pharmacokinetic sampling
  • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Statistical Center in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
  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: NCT00608361

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
Los Angeles County-USC Medical Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Kansas
Hays Medical Center
Hays, Kansas, United States, 67601
Promise Regional Medical Center-Hutchinson
Hutchinson, Kansas, United States, 65702
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Olathe Cancer Center
Olathe, Kansas, United States, 66061
Via Christi Hospital-Pittsburg
Pittsburg, Kansas, United States, 66762
Salina Regional Health Center
Salina, Kansas, United States, 67401
Saint Francis Hospital and Medical Center - Topeka
Topeka, Kansas, United States, 66606
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Missouri
Truman Medical Center
Kansas City, Missouri, United States, 64108
United States, Texas
Audie L Murphy Veterans Affairs Hospital
San Antonio, Texas, United States, 78209
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
University Hospital
San Antonio, Texas, United States, 78229
Scott and White Memorial Hospital
Temple, Texas, United States, 76508
United States, Washington
Swedish Medical Center-Edmonds
Edmonds, Washington, United States, 98026
Swedish Cancer Institute-Issaquah
Issaquah, Washington, United States, 98029
Swedish Medical Center-First Hill
Seattle, Washington, United States, 98122-4307
Swedish Medical Center-Ballard Campus
Seattle, Washington, United States, 98107
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Investigators
Principal Investigator: John Sarantopoulos Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00608361     History of Changes
Other Study ID Numbers: NCI-2009-00792, NCI-2009-00792, CDR0000583976, SWOG-S0711, S0711, S0711, U10CA032102, U10CA180888
Study First Received: January 30, 2008
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Carcinoma, Hepatocellular
Hodgkin Disease
Immunoblastic Lymphadenopathy
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Large Granular Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Liver Neoplasms
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphomatoid Granulomatosis
Mycoses
Mycosis Fungoides
Precursor Cell Lymphoblastic Leukemia-Lymphoma

ClinicalTrials.gov processed this record on October 20, 2014