allowed)
- Total serum bilirubin ≤ 1. 5xULN for age
- SGPT (ALT) ≤ 2. 5 x ULN and SGOT (AST) ≤ 2. 5 x ULN
- Serum albumin ≥ 20 g/L
- Adequate systolic ventricular function
- QTc measured by ECG must be < 450 msec.
- No history of MI, severe or unstable angina, peripheral vascular disease, or
familial QTc prolongation
- Blood pressure ≤ 95th percentile for age, height, gender AND one of:
- No current anti-hypertensive therapy, OR on stable doses of no more than one
anti-hypertensive medication
- Subjects with known history of seizures must have well-controlled seizures and
not receiving enzyme-inducing anti-convulsants
- INR ≤ 1. 2 and PTT ≤ 1. 2xULN
5. Prior Therapy
- Myelosuppressive chemo must not have been given within 3 weeks of study
enrolment (6 weeks if nitrosourea)
- At least 7 days must have elapsed since completion of therapy with a growth
factor that supports platelet or white cell number or function. At least 14
days must have elapsed after receiving pegfilgrastim.
- Biologic anti-neoplastic agent (including VEGF-blocking TKI) must not have been
administered within 7 days of study enrolment
- At least 3 half lives of the monoclonal antibody must have elapsed since the
last dose administered
- ≥ 2 weeks must have elapsed since local palliative XRT (small port); > 13 weeks
since prior total body irradiation (TBI), craniospinal XRT or > 50% radiation of
pelvis; or > 6 weeks if other substantial bone marrow irradiation
- ≥ 8 weeks must have elapsed since MIBG therapy for neuroblastoma
- At least 60 days must have elapsed from autologous or allogeneic stem cell
transplant with no signs of GVHD.
- At least 28 days from major surgery and wounds must be healed. At least 7 days
from open and/or core biopsy.
6. Ability to take liquid medication by mouth
EXCLUSION:
1. Patients with DIPG, or known CNS metastases
2. Pregnancy, breast feeding, or unwillingness to use effective contraception during the
study
3. Subjects currently receiving:
- Corticosteroids who haven't been on a stable or decreasing dose of
corticosteroid for 7 days prior
- Another investigational drug; other anti-cancer agents or radiation therapy
- More than one medication for blood pressure control
- Therapeutic anticoagulation, including systemic use of warfarin, heparin, or low
molecular weight heparin at any dose
- Aspirin, and/or ibuprofen, or other NSAIDs
- Drugs metabolized through several of the specific P450 cytochrome isoforms and
those receiving drugs with a known risk of torsades de pointes
- Subjects who require thyroid replacement therapy are not eligible if they have
not been receiving a stable replacement dose for at least 4 weeks prior to study
enrolment.
4. Subjects who have an uncontrolled infection; serious or non-healing wound, ulcer, or
bone fracture
5. Evidence of active bleeding, intratumoral haemorrhage, or bleeding diathesis
6. Major surgical procedure, laparoscopic procedure, open biopsy or significant
traumatic injury within 28 days prior to Day 1 therapy
7. Previous, documented hypersensitivity reactions to topotecan or pazopanib
8. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28
days of study enrolment