Sorafenib (BAY 43-9006) to Treat Children With Solid Tumors or Leukemias
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ClinicalTrials.gov Identifier: NCT01445080 |
Recruitment Status
:
Completed
First Posted
: October 3, 2011
Last Update Posted
: August 7, 2017
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Tracking Information | ||||
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First Submitted Date ICMJE | September 30, 2011 | |||
First Posted Date ICMJE | October 3, 2011 | |||
Last Update Posted Date | August 7, 2017 | |||
Study Start Date ICMJE | August 23, 2006 | |||
Actual Primary Completion Date | June 14, 2012 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Not Provided | |||
Change History | Complete list of historical versions of study NCT01445080 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Not Provided | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Sorafenib (BAY 43-9006) to Treat Children With Solid Tumors or Leukemias | |||
Official Title ICMJE | A Phase I/II Study of the RAF Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib (BAY 43-9006, NSC# 724772 IND# 69896) in Children With Refractory Solid Tumors or Refractory Leukemias | |||
Brief Summary | Background:
Objectives:
Eligibility: -Patients between 2 and 21 years of age with solid tumors or leukemias that do not respond to standard treatment. Patients between 2 and 21 years of age with AML and FLT3-ITD mutation for Part C of the study. Design:
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Detailed Description | Background: The ras gene product plays a critical role in cell signal transduction. Activating Ras mutations occur in 30% of all human cancers, and the ras pathway may be upregulated in absence of ras mutations. Activated Ras initiates several signaling cascades, and the best characterized is the Ras/Raf/MEK/ERK cascade. Ras initiates this pathway by recruiting Raf kinase to the plasma membrane where it is further modified for full activation. A high frequency of B-Raf mutations has recently been reported in a variety of adult solid cancers. Sorafenib (BAY 43-9006) is a novel, orally bioavailable, bi-aryl urea, which potently inhibits wild type and mutant raf. In addition, sorafenib inhibits several receptor tyrosine kinases including human VEGFR-2, FLT3, c-KIT, and p38 alpha, suggesting that sorafenib may mediate anti-tumor activity via several additional mechanisms. In early adult clinical trials sorafenib has been well tolerated, with minimal myelosuppression. Dose-limiting toxicities were hand-foot syndrome, diarrhea, fatigue, hypertension, pain, and rash. Responses to sorafenib have been observed in early clinical trials in adults with a variety of tumors, including tumors that have not been described to harbor raf mutations. Sorafenib recently was approved by the Food and Drug Administration for treatment of refractory renal cell cancer. OBJECTIVES: To determine the maximum tolerated dose (MTD) of oral Sorafenib in children with refractory solid tumors or refractory leukemias. To define the toxicities and pharmacokinetics of Sorafenib. To evaluate the tolerability, pharmacokinetics, pharmacodynamics and activity of sorafenib administered at the MTD for refractory leukemias in patients with AML and FLT3-ITD mutations ELIGIBILITY: Patients (greater than or equal to 24 months to less than or equal to 21 years) with refractory solid tumors or refractory leukemias. Patients (greater than or equal to 24 months to less than or equal to 21 years) with AML and FLT3-ITD mutation (Part C). Participation in pharmacokinetic sampling is mandatory for Part C. DESIGN: Sorafenib will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment cycle). Dose escalations will be performed to define the MTD. Initially, the spectrum of toxicity and MTD will be defined in patients with solid tumors. Patients with refractory leukemias will be entered at the solid tumor MTD, to determine whether patients with leukemia tolerate this dose level. Pharmacokinetics, pharmacodynamics, and pharmacogenetics of sorafenib will be studied in patients with solid tumors and leukemias. In Part C: 14 patients will receive sorafenib at 150 mg/m(2)/dose, BID to evaluate the tolerability, pharmacokinetics, pharmacodynamics and activity of sorafenib. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Sorafenib
Administered orally BID continuously. 28 days will be considered a cycle |
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Study Arms |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
2 | |||
Original Estimated Enrollment ICMJE |
77 | |||
Actual Study Completion Date | June 14, 2012 | |||
Actual Primary Completion Date | June 14, 2012 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE |
All clinical and laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. If more than 7 calendar days elapse between the date eligibility studies outlined in Section 4.1.7 were obtained and the start date of treatment, then the following studies must be repeated prior to treatment: CBC with differential, bilirubin, ALT (SGPT) and serum creatinine, lipase and amylase. If any of these repeat laboratory studies are outside the parameters required for eligibility (labs may again be repeated within 48-72 hours), then the patient is off protocol therapy. Imaging and bone marrow studies are required within 2 weeks prior to the start of protocol therapy. The eligibility criteria listed below are interpreted literally and cannot be waived (per COG policy posted 5/11/01). All clinical and laboratory data required for determining eligibility of a patient enrolled on this trial must be available in the patient's medical or research record which will serve as the source document for verification at the time of audit. INCLUSION CRITERIA (refers to both Parts A, B and C of the study, unless otherwise indicated): Age: Patients must be greater than or equal to 24 months and less than or equal to 21 years of age at the time of study enrollment. Diagnosis: Part A: Patients with Solid Tumors Patients with solid tumors must have had histologic verification of solid tumor malignancy at either original diagnosis or relapse. Part B Patients with Leukemias Patients with leukemias must have histologically-confirmed acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), juvenile myelomonocytic leukemia (JMML), or chronic myelogenous leukemia (CML) in blast crisis. Part C: Patients with AML and FLT3-ITD mutation Patients must have AML and documentation of a FLT3-ITD mutation by a CLIA certified laboratory. DISEASE STATUS: Part A: Patients with Solid Tumors Patients with solid tumors must have either measurable or evaluable disease. Part B: Patients with Leukemias Patients with leukemias must have greater than 25% blasts in the bone marrow (M3 bone marrow). Active extramedullary disease (except for leptomeningeal disease) may also be present. Patients with JMML have to meet diagnostic criteria for JMML, and the requirement of greater than 25% blasts in the bone marrow does not apply to patients with JMML. Part C: Patients with AML and FLT3-ITD mutation Patients must have greater than or equal to 5% blasts in the bone marrow. Active extramedullary disease (except for leptomeningeal disease) may also be present. Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life. Performance Level: Karnofsky greater than or equal to 50% for patients greater than 10 years of age and Lansky greater than or equal to 50 for patients less than or equal to 10 years of age. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. PRIOR THERAPY: Part A - Patients with Solid Tumors Patients with solid tumors must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. The Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used for toxicity assessment. A copy of the CTCAE version 3.0 can be downloaded from the CTEP home page (http://ctep.info.nih.gov). Recovery is defined as a toxicity Grade less than 2, unless otherwise specified in the Inclusion and Exclusion Criteria. For patients with solid tumors the following applies:
Part B: Patients with Leukemias: Patients with leukemias must have recovered from the non hematologic toxic effects of all prior therapy before enrollment onto this trial. The Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used for toxicity assessment. A copy of the CTCAE version 3.0 can be downloaded from the CTEP home page (http://ctep.info.nih.gov). Recovery is defined as a toxicity Grade less than 2, unless otherwise specified in the Inclusion and Exclusion Criteria. For patients with leukemia the following applies:
Part C: Patients with AML and FLT3-ITD mutation Patients with FLT3-ITD AML who relapse while receiving maintenance-like low dose chemotherapy such as dexamethasone/thioguanine, oral etoposide, or decitabine will not be required to have a waiting period before enrollment onto this study provided they meet all other inclusion criteria. (For questions regarding whether a current chemotherapy regimen can be considered maintenance like therapy, please contact the study chair to discuss prior to enrollment.) Patients who are refractory or who relapse while not receiving maintenance-1ike therapy must have recovered from the non-hematologic toxic effects of all prior therapy before enrollment onto this trial. The Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 will be used for toxicity assessment. A copy of the CTCAE version 3.0 can be downloaded from the CTEP home page (http://ctep.info.nih.gov). Recovery is defined as a toxicity Grade less than 2, unless otherwise specified in the Inclusion and Exclusion Criteria. For such patients with AML and FLT3-ITD mutation the following applies:
Organ Function Requirements Adequate Bone Marrow Function Defined As:
Blood counts are not required to be normal prior to enrollment on this trial. However, platelet count has to be greater than or equal to 20,000/mm(3) (may receive platelet transfusions) Adequate Renal Function Defined as:
Age 2 to less than 6 years = Maximum Serum Creatinine (mg/dL) male 0.8 and female 0.8. Age 6 to less than 10 years = Maximum Serum Creatinine (mg/dL) male 1 and female 1. Age 10 to less than 13 years = Maximum Serum Creatinine (mg/dL) male 1.2 and female 1.2. Age 13 to less than 16 years = Maximum Serum Creatine (mg/dL) male 1.5 and female 1.4. Age greater than or equal to 16 years = Maximum Serum Creatinine (mg/dL) male 1.7 and female 1.4. The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined As:
Normal PT, PTT, and INR for patients on prophylactic anticoagulation only. Normal serum lipase and amylase. Adequate Pulmonary Function Defined As: No evidence of dyspnea at rest, no exercise intolerance and a pulse oximetry greater than 94% if there is clinical indication for determination. For Part A and B Only: Diastolic Blood Pressure Within The Upper Limit Of Normal Defined As: A diastolic blood pressure (DBP) less than or equal to the 95th percentile for age and gender (Appendix V) measured as in Section 8.1 of the protocol and not be receiving medication for treatment of hypertension. For Part C only: Blood Pressure Within the Upper Limit of Normal Defined As: A blood pressure (BP) ... |
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Sex/Gender |
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Ages | 2 Years to 21 Years (Child, Adult) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01445080 | |||
Other Study ID Numbers ICMJE | 060233 06-C-0233 |
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Has Data Monitoring Committee | Not Provided | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) | |||
Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | |||
Verification Date | July 28, 2017 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |