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

June 30, 2015 updated by: National Cancer Institute (NCI)

Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles County-USC Medical Center
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
    • Kansas
      • Hays, Kansas, United States, 67601
        • Hays Medical Center
      • Hutchinson, Kansas, United States, 67502
        • Hutchinson Regional Medical Center
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Olathe, Kansas, United States, 66061
        • Olathe Cancer Center
      • Pittsburg, Kansas, United States, 66762
        • Via Christi Hospital-Pittsburg
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Topeka, Kansas, United States, 66606
        • Saint Francis Hospital and Medical Center - Topeka
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center
    • Texas
      • San Antonio, Texas, United States, 78229
        • University Hospital
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
      • San Antonio, Texas, United States, 78209
        • Audie L Murphy Veterans Affairs Hospital
      • Temple, Texas, United States, 76508
        • Scott and White Memorial Hospital
    • Washington
      • Edmonds, Washington, United States, 98026
        • Swedish Medical Center-Edmonds
      • Issaquah, Washington, United States, 98029
        • Swedish Cancer Institute-Issaquah
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98107
        • Swedish Medical Center-Ballard Campus
      • Seattle, Washington, United States, 98122-4307
        • Swedish Medical Center-First Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: Pharmacological Study
Correlative studies
Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Toxicity will be graded according to the NCI CTCAE v3.0.
28 days
Pharmacokinetic parameters of dasatinib
Time Frame: Days 1 and 8 of course 1
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).
Days 1 and 8 of course 1

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver dysfunction data
Time Frame: Baseline
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.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: John Sarantopoulos, Southwest Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (ACTUAL)

August 1, 2014

Study Completion (ACTUAL)

August 1, 2014

Study Registration Dates

First Submitted

January 30, 2008

First Submitted That Met QC Criteria

January 30, 2008

First Posted (ESTIMATE)

February 6, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

July 2, 2015

Last Update Submitted That Met QC Criteria

June 30, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00792 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • U10CA032102 (U.S. NIH Grant/Contract)
  • U10CA180888 (U.S. NIH Grant/Contract)
  • CDR0000583976
  • SWOG-S0711
  • S0711 (OTHER: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Recurrent Adult Burkitt Lymphoma

Clinical Trials on Pharmacological Study

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe