Pazopanib Paediatric Phase II Trial Children's Oncology Group (COG) in Solid Tumors
Condition: Solid Tumours
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The study design was an open-label Phase II pediatric clinical study. The purpose of Study
      X2203 was to identify any efficacy signal in subjects with the disease subtypes under study,
      when treated with pazopanib monotherapy. Furthermore, it was to define the toxicities of
      pazopanib in children, as well as examine biological markers, e.g. cytokines and angiogenic
      factors, that could help further characterize any response of pazopanib in children.
      Pazopanib was administered as monotherapy in tablet and powder suspension formulations at
      daily doses of 450 mg/m2/dose or 225 mg/m2/dose, respectively. The first 6 enrolled subjects
      receiving oral suspension formulation were assessed for tolerability and extended PK
      sampling; and, only if pazopanib was tolerated, subsequent subjects were enrolled at the same
      starting dose with the suspension. Dose escalation was not permitted. For the tablet, a
      dosing nomogram was used based on the subject's BSA. Dose reduction was dependent upon the
      toxicity of pazopanib and disease status of the infants, toddlers, children, adolescents, and
      young adults. Subjects could be as young as 1 year-old infants to screen for enrollment.
      Subjects were assessed for initial response after 8 weeks of treatment prior to Cycle 3. A
      cycle was defined as 28 days of pazopanib treatment with no rest period between cycles.
      Treatment was administered continuously once daily. Treatment was to be discontinued if there
      was evidence of disease progression, unacceptable treatment-related toxicity, pregnancy.
      Histological classification was an important diagnostic inclusion in these subjects with a
      wide variety of refractory solid tumors, i.e. 7 different tumor types and each being a
      cohort.
    

Detailed description: 
      The study design included a hierarchical 2-stage tumor response assessment with each cohort
      independent from one other. First, an initial 10 subjects were enrolled into each cohort. In
      the event of ≥ 1 response in any of these initial subjects, an additional 10 subjects may be
      enrolled in that cohort to proceed. In the event of ≥ 3 responses, the agent was considered
      effective. However after end of-stage 1, study enrollment stopped due to insufficient
      antitumor activity. Subjects who discontinued study treatment were followed for survival
      status. The study was to continue accruing data and thus, remained open for approximately 1
      year from Last Subject Last Visit (LSLV).
    

Intervention name(s): Pazopanib
Intervention type(s): Drug
Intervention description(s): Pazopanib was supplied as a series of aqueous film-coated tablets containing 200 mg (oval-shaped, white, packaged in bottles containing 34 tablets each), and 400 mg (oval-shaped, white, packaged in bottles containing 68 tablets each). Pazopanib Powder for Oral Suspension was a white to slightly colour powder supplied to the clinical sites in amber glass (United State Pharmacopeia (USP) Type III) bottles with child-resistant closures. Each bottle contains 5 g of pazopanib.
Other intervention name(s): GW786034
Intervention model: Single Group Assignment
Intervention model description: The study design included a hierarchical 2-stage tumor response assessment with each cohort independent from one other.
Cohort 1: rhabdomyosarcoma (RMS)
Cohort 2: non-rhabdomyosarcomatous soft tissue sarcoma (NRSTS)
Cohort 3: Ewing sarcoma/pPNET
Cohort 4: osteosarcoma
Cohort 5: measurable neuroblastoma (mNeuroblastoma)
Cohort 6: evaluable neuroblastoma (eNeuroblastma)
Cohort 7: hepatoblastoma
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: VEGF; Pazopanib; Sarcoma; GW786034; Refractory Solid Tumors