A phase II study of pazopanib in children, adolescents, and young adults with refractory solid tumors.
Bibliographic record
Abstract
TPS10081 Background: Pazopanib (VOTRIENT; GlaxoSmithKline) is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and c-Kit, and is indicated for the treatment of adults with advanced RCC and advanced soft tissue sarcoma. Data from adults with sarcoma support the study of soft tissue and bone sarcomas, as well as embryonal tumors, in pediatric subjects. The current Phase II study undertaken by the Children’s Oncology Group (COG-ADVL1322/ VEG116731) was preceded by a Phase I trial of pazopanib tablets and powder for oral suspension (PfOS) in children (N = 51). The maximum tolerated dose (MTD) for tablets was 450 mg/m2/dose and 160 mg/m2/dose for the PfOS, with two dose-limiting toxicities (DLTs) seen at 225 mg/m2 of the PfOS. Hematologic and non-hematologic toxicities were generally mild. One subject each with hepatoblastoma or desmoplastic small round cell tumor had a partial response; 8 had stable disease ( ≥ 6 cycles); 7 of these had sarcoma (Glade Bender; J. Clin. Oncol. 2013; 31:3034). Given these findings, this Phase II trial will further evaluate efficacy, safety, pharmacokinetics, and pharmacodynamics in children. Methods: This is a multi-center study of pazopanib in US and Canadian subjects age 1 to 18 years with solid tumors relapsed or refractory to prior therapy. Tumor types include rhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, and hepatoblastoma. Subjects will be stratified by tumor type, and the response rate to pazopanib will be assessed for each of the six disease strata using a two-stage design. Pazopanib will be administered orally once daily as a tablet at 450 mg/m2 or as PfOS at 225 mg/m2. The phase I PfOS MTD of 160 mg/m2 may result in suboptimal exposure. Given that the toxicity at 225mg/m2 was isolated and reversible, the first 6 patients receiving PfOS will be dosed at 225 mg/m2 and assessed for first-cycle DLTs and PK. The study will also evaluate pazopanib pharmacokinetics and toxicity in this pediatric population and will assess the relationship between efficacy and levels of cytokines and angiogenic factors, and VEGF and KDR polymorphisms. Four of 77 subjects have been enrolled. (NCT01956669) Study funded by GSK. Clinical trial information: NCT01956669.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".