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NRG/RTOG 0912

A Randomized Phase II Study of Concurrent Intensity Modulated Radiation Therapy (IMRT), Paclitaxel and Pazopanib (NSC 737754)/Placebo, for the Treatment of Anaplastic Thyroid Cancer

Phase 2N = 89NCT01236547

Population
Adults with pathologically diagnosed anaplastic thyroid cancer of any TNM stage, Zubrod performance status 0 to 2, no recent haemoptysis or bleeding and no brain metastases
Design
Randomised (1:1), double-blind, placebo-controlled multicentre phase 2 trial at 34 US centres of concurrent weekly paclitaxel and intensity-modulated radiotherapy (66 Gy in 33 fractions) with pazopanib or placebo, after a safety run-in. Primary end point overall survival (intention-to-treat population), one-sided log-rank test. Randomisation was stratified by metastatic disease.
Primary endpoint
OS
Arms
  • Paclitaxel and IMRT with pazopanib (experimental, n = 36): Paclitaxel (weekly) with pazopanib daily and IMRT 66 Gy in 33 fractions
  • Paclitaxel and IMRT with placebo (control, n = 35): Paclitaxel (weekly) with matching placebo and IMRT 66 Gy in 33 fractions
People
Sherman EJ
OSHR 0.86 (95% CI 0.52–1.43)Δ median OS−1.6 monthsΔ 12-month OS+8.1 points
Show the numbers
Results reported for NRG/RTOG 0912
EndpointAnalysisPaclitaxel and IMRT with pazopanibPaclitaxel and IMRT with placeboEffect
OSEligible randomised patients (71: 36 pazopanib, 35 placebo), the protocol-specified primary analysis population (the full text calls it eligible intention-to-treat)finalmedian follow-up 2.9 yearsSherman 2023median 5.7 months (4.0–12.8); 37.1% at 12 mo (21.1–53.2%)median 7.3 months (4.3–10.6); 29% at 12 mo (13.2–44.8%)HR 0.86 (95% CI 0.52–1.43)P=0.28One-sided log-rank p-value. Median follow-up 2.9 years (IQR 0.002 to 4.0); 61 patients had died at the final analysis. Overall survival was not significantly improved with pazopanib.
Results reported for NRG/RTOG 0912
EndpointAnalysisPaclitaxel and IMRT with pazopanibPaclitaxel and IMRT with placeboEffect
OSEligible randomised patients (71: 36 pazopanib, 35 placebo), the protocol-specified primary analysis population (the full text calls it eligible intention-to-treat)finalmedian follow-up 2.9 yearsSherman 2023median 5.7 months (4.0–12.8); 37.1% at 12 mo (21.1–53.2%)median 7.3 months (4.3–10.6); 29% at 12 mo (13.2–44.8%)HR 0.86 (95% CI 0.52–1.43)P=0.28One-sided log-rank p-value. Median follow-up 2.9 years (IQR 0.002 to 4.0); 61 patients had died at the final analysis. Overall survival was not significantly improved with pazopanib.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.860.52–1.43
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%051015Months (modelled)
  • Paclitaxel and IMRT with pazopanib (experimental)
  • Paclitaxel and IMRT with placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPaclitaxel and IMRT with pazopanibPaclitaxel and IMRT with placebo
0100.0%100.0%
554.4%62.2%
933.5%42.5%
1418.2%26.5%
1811.2%18.1%
Primary publication: Sherman EJ, Harris J, Bible KC, Xia P, Ghossein RA, Chung CH, et al. Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial. Lancet Oncol. 2023;24(2):175-186. PubMedDOI

Appears in

Sources

  1. Sherman EJ, Harris J, Bible KC, Xia P, Ghossein RA, Chung CH, et al. Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial. Lancet Oncol. 2023;24(2):175-186.

    PubMedDOI