Safety, tolerability and pharmacokinetics of regorafenib in pediatric subjects.
- Conditions
- Pediatric patients with solid malignant tumors that are recurrent or refractory to standard therapy.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003579-36-IT
- Lead Sponsor
- Bayer HealthCare AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 50
- Signed Informed Consent Form by subjects and/or subjects’ parents/legal guardians and age appropriate Assent Form by the subjects obtained before any study specific procedure
- Age: from 5 years to less than 18 years old
- Pediatric subjects who are able to swallow tablets
- Diagnosis: subjects must have had histologic verification of solid malignancy at original diagnosis. Subjects with recurrent or refractory solid tumors are eligible, including primary CNS tumors or subjects with known CNS metastases
- Subject’s current disease state must be one for which there is no known effective therapy or therapy proven to prolong survival with an acceptable quality of life. Effective therapy may include surgery, radiation therapy, chemotherapy or any combination of these modalities.
- Sexually active females of childbearing potential and sexually active males must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration. Abstinence is considered an adequate contraception method. For sexually active females, 2 forms of highly effective contraception are mandatory. The investigator or a designated associate is requested to advise the subject on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically
recommended method (or combination of methods) as per standard of care.
- Female subjects of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment.
- Subjects must have at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. For neuroblastoma subjects with osteomedullary disease, the SIOPEN (International Society of Pediatric Oncology Europe Neuroblastoma Group) score will be used.
- Life expectancy of at least 12 weeks from the time of signing informed
consent/assent
- Performance level: Karnofsky = 70% for subjects > 10 years of age and Lansky = 70% for subjects = 10 years of age, except children with motor paresis due to disease. Neurological deficits in subjects must have been stable for a minimum of 1 week prior to first dose of study treatment.
- Subjects with brain tumors or brain metastases must be on stable dose of corticosteroids for at least 1 week prior to first dose of study treatment.
- Adequate hematological function assessed by the following laboratory
requirements conducted within 7 days before starting study treatment:
o Peripheral absolute neutrophil count (ANC): = 1.0 x 10 9/L
o Platelet count : = 100 x 109/L (transfusion independent)
o Hemoglobin : = 8.0 g/ dL
- Adequate renal function defined as creatinine clearance based on Schwartz Estimate = 70 ml/min/1.73 m2 (1)
- International normalized ratio (INR) = 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) = 1.5 x ULN
- Lipase = 1.5 x ULN
- Adequate hepatic function defined as:
o Aspartate aminotransferase/alanine aminotransferase (AST/ALT)
=3.0 x ULN
o Bilirubin (sum of conjugated and unconjugated) = 1.5 ULN
o Alkaline phosphatase limit = 2.5 x ULN for age (= 5 x ULN for
subjects with bone tumors)
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) no
F.1.2.1 Numb
- Prior treatment with regorafenib. Subjects permanently withdrawn from study participation will not be allowed to re-enter the study.
- Active or uncontrolled infection (> National Cancer Institute Common
Terminology Criteria for Adverse Events [NCI-CTCAE] Grade 2 at screening).
- Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
- Known history of human immunodeficiency virus (HIV) infection
- Major surgical procedure or significant traumatic injury within 28 days before start of study medication. Bone marrow biopsy and central lines will not be considered as a major surgical procedure.
- Non-healing wound, ulcer, or bone fracture
- Seizure disorder requiring medication with: carbamazepine, phenobarbital, phenytoin, ethosuximide, valproic acid, tiagabine, felbamate, tiagabine, zomisamide and lamotrigine. Subjects with history of seizures controlled with levetiracetam or gabapentin and subjects with brain tumors receiving prophylactic levetiracetam or gabapentin are allowed to enter the study.
- Subjects with uncontrolled baseline hypertension higher than Grade 1 NCICTCAE v.4.0 (recurrent or persistent [=24 hours] blood pressure [BP] >ULN: BP > the 95th percentile for age, height, and gender measured as described in Appendix 14.5). Additional information about hypertension is provided in Appendix 14.6.
- Clinically significant bleeding (NCI-CTCAE v. 4.0 Grade 3 or higher) within 30 days before start of study medication
- Arterial or venous thrombotic or embolic events such as deep vein thrombosis or pulmonary embolism within 6 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the start of study medication)
- Subjects with evidence or history of disorders of coagulation or thrombosis
- Cardiac abnormalities such as congestive heart failure (Modified Ross Heart Failure Classification for Children = class 2) and cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- History of organ allograft (including allogeneic bone marrow transplant)
- Unresolved toxicity higher than NCI-CTCAE v. 4.0 Grade 1 attributed to any prior therapy/procedure (excluding alopecia, chemotherapy-induced ototoxicity, Grade 2 chemotherapy-induced neuropathy and, as per above eligibility criteria, anemia with hemoglobin = 8 mg/dL and ANC = 1.0 x 10 9/L )
- Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE v. 4.0 Grade 2 dyspnea)
- Known hypersensitivity to any of the study drugs, study drug classes, or
excipients in the formulation
- Pregnancy or breast feeding
- Significant gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn’s disease or any malabsorption condition
- Interstitial lung disease with ongoing signs and symptoms at the time of screening
- Any other serious or unstable illness, or medical, psychological or social
condition, that could jeopardize the safety of the subject and/or his/her
compliance with study procedures, or may interfere with the subject’s
participation in the study or evaluation of the study results
- Close affiliation with the investigational site, e.g. a close relative of the
investigator or a dependent person (e.g. employee or student of the
investigational site)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method