viernes, 8 de julio de 2016

NCT02747537 Clinical Trial - National Cancer Institute || Sorafenib Tosylate and Irinotecan Hydrochloride in Treating Pediatric Patients with Recurrent or Refractory Solid Tumors

NCT02747537 Clinical Trial - National Cancer Institute

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Sorafenib Tosylate and Irinotecan Hydrochloride in Treating Pediatric Patients with Recurrent or Refractory Solid Tumors

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Tissue collection/RepositoryActive2 to 24201605006
NCI-2016-00680, NCT02747537

Trial Description


This phase II trial studies how well sorafenib tosylate and irinotecan hydrochloride work in treating pediatric patients with solid tumors that have returned after a period of improvement or have not responded to previous treatment. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving sorafenib tosylate and irinotecan hydrochloride may work better in treating pediatric patients with recurrent or refractory solid tumors.

Further Study Information

I. To determine the response rate of relapsed, recurrent, or refractory pediatric tumors possessing a non-synonymous mutation in v-RAF murine leukemia viral oncogene homolog (Raf), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), fms-related tyrosine kinase 3 (Flt-3), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), retrovirus associated sequence (RAS), mitogen-activated protein kinase kinase (MEK), or extracellular signal-regulated kinase (ERK) to the combination of sorafenib and irinotecan.
I. To determine the time to progression of patients receiving this treatment regimen.
II. To further define and describe the scope of toxicities of patients receiving multiple cycles of this regimen.
Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-21 and irinotecan hydrochloride PO on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, and every month for up to 3 months.

Eligibility Criteria

Inclusion Criteria:
Relapsed, refractory, or recurrent malignancy; all solid tumor diagnoses will be eligible
Pathologic confirmation of the diagnosis either at original diagnosis or recurrence
Known non-synonymous mutation in the following genes: Raf, PDGFR, VEGFR, Flt-3, KIT, JAK, STAT, RAS, MEK, or ERK; genomic sample preferably from relapse, but may be from other stage of treatment if relapse sample is not reasonably obtainable; genetic analysis for determination of eligibility occurs as part of routine care and is not being performed specifically for the purposes of this study
Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) or magnetic resonance imaging (MRI) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam
Prior therapy
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
Hematopoietic growth factors: At least 14 days must have elapsed after receiving pegfilgrastim and least 7 days must have elapsed since the completion of therapy with a non-pegylated growth factor
Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
Radiotherapy: >= 2 weeks must have elapsed since local palliative external beam radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of metaiodobenzylguanidine (MIBG); >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
Stem cell transplant or rescue without TBI: No evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant
Patients must have a performance status corresponding to Karnofsky or Lansky greater than or equal to 50%; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; 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
Absolute neutrophil count >= 1,000/mcl
Platelets >= 75,000/mcl (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
Total bilirubin =< institutional upper limit of normal (IULN)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase(ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
Note: For the purposes of this trial the ULN for ALT is defined as 45 U/L
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
2 to < 6 years: maximum serum creatinine 0.8 mg/dL (male and female)
6 to < 10 years: maximum serum creatinine 1 mg/dL (male and female)
10 to < 13 years: maximum serum creatinine 1.2 mg/dL (male and female)
13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
>= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Partial thromboplastin time (PTT) < IULN
International normalized ratio (INR) < IULN or prothrombin time (PT) < IULN
Normal serum lipase and amylase (per institutional normal values)
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94%
Shortening fraction >= 28% or ejection fraction (LVEF) >= 55%, as well as
A blood pressure (BP) =< the 95th percentile for age, height, and gender and not receiving medication for treatment of hypertension
Normal electrocardiogram with corrected QT (QTc) =< 450
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
Exclusion Criteria:
Patients who have received a cumulative doxorubicin equivalent of > 375 mg/m^2 total lifetime dose
Patients who have had or are planning to have the following invasive procedures are not eligible:
Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 14 days prior to initiation of protocol therapy; there should be no anticipation of need for major surgical procedures during the course of the study
Central line placement or subcutaneous port placement is not considered major surgery; external central lines must be placed at least 3 days prior to initiation of protocol therapy and subcutaneous ports must be placed at least 7 prior to initiation of protocol therapy
Patients must not be on therapeutic anti-coagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial devices is allowed provided that the requirements for PT, INR, and PTT are met
Patients with evidence of bleeding diathesis are not eligible
Patients with known Gilbert syndrome are not eligible
A history of other malignancy =< 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
Currently receiving any other investigational agents
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib or irinotecan
Currently on the following concomitant medications or substances that have the potential to affect the activity or pharmacokinetics of the study drug(s); the use of the following medications should be discontinued prior to initiation of protocol therapy and should be avoided during protocol therapy if reasonable alternatives exist
Corticosteroids: Patients requiring corticosteroids that have not been on a stable or decreasing dose of corticosteroid for 7 days prior to enrollment are not eligible
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, prolonged QTc, interstitial lung disease, gastrointestinal perforation, hepatic impairment/failure, or renal impairment/failure
Pregnant and/or breastfeeding; women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of study entry
Known human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Siteman Cancer Center at Washington University

  • National Cancer Institute
Robert J. Hayashi, Principal Investigator
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the record via the link above for more information about participating sites.

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