A Phase 1, Open-label , Dose EscalationStudy of Berubicin® in Pediatric Patientswith Progressive, Refractory, or Recurrent High GradeGliomas
- Conditions
- High Grade GliomasTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004016-58-PL
- Lead Sponsor
- WPD Pharmaceuticals Sp. z o.o.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 35
1.Written informed consent of the patient’s LAR, and assent when
appropriate based on the patient’s age and institutional guidelines, prior
to any study-related procedure.
2. Patients must have progressive, refractory, or recurrent HGG (WHO
Grade III or IV).
3. Age =2 to <18 years at the tiem of the first Berubicin dose.
4. Performance status score =50 (Lansky for research patients aged
=16 years and Karnofsky for patients ?16 years). 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.
5. Patients must have completed at least 1 line of prior therapy.
6. Before the projected start of scheduled study treatment, the following
time periods must have elapsed:
a. 5 half-lives from any investigational agent.
b. 4 weeks from cytotoxic therapy (except 23 days from
temozolomide and 6 weeks from nitrosoureas).
c. 6 weeks from antibody therapies.
d. 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor
therapies.
e. Patients who have received radiation therapy must be =6 weeks
post the completion of local palliative radiation therapy (reirradiation
for progressive disease or upfront radiation therapy at
initial diagnosis).
7. Adequate organ function defined as:
a. Bone marrow:i. Peripheral absolute neutrophil count =1000/mm3
ii. Hemoglobin =8 g/dL (may have received packed red blood cell
transfusion)
iii. Platelet count =100,000/mm3 (transfusion-independent, defined
as not receiving platelet transfusions for at least 7 days prior to
enrollment)
b. Renal function:
i. Creatinine clearance or radioisotope glomerular filtration rate
=70 mL/min/1.73 m2 or normal serum creatinine based on age
as shown below:
? Age <5 years: 0.8 mg/dL maximum
? Age =5 to <10 years: 1.0 mg/dL maximum
? Age =10 to <15 years: 1.2 mg/dL maximum
? Age =15 years: 1.5 mg/dL maximum
c. Hepatic function:
i. Total bilirubin (sum of conjugated + unconjugated) =1.5 × the
upper limit of normal (ULN) for the institution
ii. Alanine aminotransferase =3 × ULN for the institution
iii. Serum albumin =2 g/dLd. Neurologic function:
i. Patients with seizure disorder may be enrolled if the seizure
disorder is well controlled, as determined by the investigator.
e. Cardiac function (left ventricular ejection fraction [LVEF]):
i. Fractional shortening =27% or LVEF =50% by echocardiogram
or multigated radionuclide study (MUGA)
8. All adverse events (AEs) Grade >1 related to prior therapies
(chemotherapy, radiation therapy, and/or surgery) must be resolved to
Grade 1 or baseline level, except for alopecia and sensory neuropathy
Grade =2 or other Grade =2 AEs not constituting a safety risk based on
the investigator's judgment.
9.For postpubertal patients: Female patients must agree to use highly
effective contraception during the period of the study and for at least
90 days after completion of treatment. Male patients must be
surgically sterile or must agree to use highly effective contraception
during the period of the study and for at least 90 days after completion
of treatment. Details are provided in the full protocol.
10. Female patients of childbearing potential aged 10 years or older must
have a negative serum or urine pregnancy test.
11. MRI of the brain and entire spine (including all sites of disease), within
10 days prior to start of study drug.
12. Corticosteroid dose must be stable or decreasing
1. Evidence of diffuse leptomeningeal disease or evidence of
cerebrospinal fluid (CSF) dissemination.
2. Known additional malignancy that is progressing or has required active
treatment within 3 years of start of study drug.
3. History of allergic reactions attributed to compounds of similar
chemical or biologic composition to Berubicin or its excipients.
4. Patients with any clinically significant, unrelated systemic illness (eg,
significant pulmonary, hepatic [including Gilbert’s syndrome], or other
organ dysfunction) or psychiatric illness/social situations that would
compromise the patient’s ability to tolerate the study drug or study
procedures or would likely interfere with the study procedures or
results.
5. Any known clinically significant active bacterial, fungal, or viral
infection including hepatitis B or hepatitis C, or any underlying disease
in the recent past that could compromise enrollment and the safety of
the patient.
6. Patient with a history of clinically significant, uncontrolled heart
disease and/or repolarization abnormalities as documented by a
standard 12-lead electrocardiogram (ECG).
7. Known history of cardiac arrhythmias including atrial fibrillation,
tachyarrhythmias, or bradycardia, unless arrhythmia is controlled and
after a cardiology consultation has cleared the patient to receive
Berubicin. Patients receiving therapeutic agents known to prolong QTinterval will be excluded; however, the use of ondansetron is permitted.
Patients with a history of congestive heart failure, myocardial
infarction, or stroke in the last 3 months will be excluded.
8. Congenital long QT syndrome or QTc >460 ms.
9. Patients receiving any other anticancer or investigational drug therapy.
10. Prior treatment with bevacizumab.
11. Current or planned participation in a study of another investigational
agent or using an investigational device.
12. Requirement for cytochrome P450 3A4 (CYP3A4)-inducing or
inhibiting agents, with the exception of corticosteroids.
Patients unable to return for follow-up visits or undergo follow-up
procedures required to assess toxicity of therapy.
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