| Title |
A Phase I and Enrichment Study of Low-dose Metronomic Topotecan and Pazopanib in Pediatric Patients With Recurrent or Refractory Solid Tumours Including CNS Tumours |
| Protocole ID |
IND.217 (TOPAZ) |
| ClinicalTrials.gov ID |
NCT02303028 |
| Cancer Type(s) |
Pediatric |
| Phase |
Phase I |
| Stage |
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| Study Type |
|
| Drug |
|
| Institution |
CENTRE HOSPITALIER UNIVERSITAIRE SAINTE-JUSTINE
|
| City |
Montréal |
| Principal Investigator |
Dr. Monia Marzouki
|
| Coordinator |
Linda Hershon
514-345-4931 poste 5899
|
| Status |
Recruiting |
| Activation Date |
|
| Eligibility Criteria |
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Disease: Part 1-Relapsed or refractory solid tumours including CNS tumours; Part 2A-Neuroblastoma, Part 2B Rhabdomyosarcoma
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Measurable or evaluable disease
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No known curative therapy, or therapy proven to prolong survival with an acceptable QOL
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Organ Function Criteria
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Peripheral ANC ≥ 1,500/μL; Plt ≥ 100,000/ and Hb ≥ 80 g/L (RBC transfusion permitted)
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Measured creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2, OR a serum creatinine based on age/gender that meets the criteria outlined in the protocol
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Urinalysis negative for protein, urine protein:creatinine ratio of ≤ 1, OR a 24-hour urine protein < 1000 mg/dL
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<Gr.1 abnormalities of K, Ca (confirmed by ionized Ca),Mg or Ph (supplementation allowed)
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Total serum bilirubin ≤ 1.5xULN for age
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SGPT (ALT) ≤ 2.5 x ULN and SGOT (AST) ≤ 2.5 x ULN
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Serum albumin ≥ 20 g/L
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Adequate systolic ventricular function (LVSF≥ 27% or LVEF ≥ 50%)
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QTc measured by ECG must be < 450 msec.
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No history of MI, severe or unstable angina, peripheral vascular disease, or familial QTc prolongation
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Blood pressure ≤ 95th percentile for age, height, gender AND one of:
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No current anti-hypertensive therapy, OR on stable doses of no more than one anti-hypertensive medication
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Subjects with known history of seizures must have well-controlled seizures and not receiving enzyme-inducing anti-convulsants
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INR ≤ 1.2 and PTT ≤ 1.2xULN
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Prior Therapy
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Myelosuppressive chemo must not have been given within 3 weeks of study enrolment (6 weeks if nitrosourea)
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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.
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Biologic anti-neoplastic agent (including VEGF-blocking TKI) must not have been administered within 7 days of study enrolment
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At least 3 half lives of the monoclonal antibody must have elapsed since the last dose administered
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≥ 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
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≥ 8 weeks must have elapsed since MIBG therapy for neuroblastoma
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At least 60 days must have elapsed from autologous or allogeneic stem cell transplant with no signs of GVHD.
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At least 28 days from major surgery and wounds must be healed. At least 7 days from open and/or core biopsy.
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Ability to take liquid medication by mouth
|
| Exclusion Criteria |
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Patients with DIPG, or known CNS metastases
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Pregnancy, breast feeding, or unwillingness to use effective contraception during the study
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Subjects currently receiving:
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Corticosteroids who haven't been on a stable or decreasing dose of corticosteroid for 7 days prior
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Another investigational drug; other anti-cancer agents or radiation therapy
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More than one medication for blood pressure control
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Therapeutic anticoagulation, including systemic use of warfarin, heparin, or low molecular weight heparin at any dose
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Aspirin, and/or ibuprofen, or other NSAIDs
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Drugs metabolized through several of the specific P450 cytochrome isoforms and those receiving drugs with a known risk of torsades de pointes
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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.
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Subjects who have an uncontrolled infection or serious non-healing would, ulcer or bone fracture.
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Evidence of active bleeding, intratumoral haemorrhage, or bleeding diathesis, hemoptysis or any evidence of GI hemorrhage.
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Major surgical procedure, laparoscopic procedure or significant traumatic injury within 28 days prior to Day 1 therapy. Open or core biopsy within 7 days prior to Day 1 of therapy.
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Previous, documented hypersensitivity reactions to topotecan or pazopanib
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History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days of study enrolment.
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Groupe d'étude en oncologie du Québec