Phase II study of XL184 (cabozantinib) in recurrent or metastatic endometrial cancer: A trial of the PMH, Chicago, and California Phase II Consortia.
Bibliographic record
Abstract
TPS5629 Background: Recurrent endometrial cancer (EC) has a poor prognosis with few therapeutic options. Targeting angiogenesis through VEGF inhibition has demonstrated real but limited efficacy. Simultaneous inhibition of angiogenesis and putative resistance mechanisms may provide more durable therapeutic responses. MET/HGF (hepatocyte growth factor) paracrine signaling has been implicated in more aggressive tumour biology, angiogenesis and resistance to VEGF targeting in EC. XL-184 (cabozantinib) is an orally bioavailable, multi-targeted inhibitor with activity against MET and VEGFR2 in addition to TIE2, RET, AXL and KIT. Methods: This phase II, multicenter single arm trial has a planned enrollment of 36 pts utilizing a Simon 2-stage design to evaluate co-primary endpoints of response rate and 12 week progression-free-survival (PFS) in pts with serous, endometrioid or mixed histology EC (experimental cohort). Eligible pts must have radiographic progression after 1 line of chemotherapy for metastatic disease, or progression within 12 months of adjuvant chemotherapy; prior radio- and hormonal therapy is allowed. Stage I has a planned accrual of 18 pts, study will proceed to stage II with observation of > 2 partial responses (PR) and > 6 12-wk PFS. Pts are also accrued to an exploratory cohort (maximum 30 pts) of rare histology EC (clear cell, carcinosarcoma). XL-184 is administered at a starting dose of 60mg orally once daily on a continuous 28 day cycle. Adverse event (AE) reporting is as per CTCAE v4.0. Pts undergo first CT evaluation after 1 cycle, those with SD or PD and ≤ grade 1 toxicity are eligible for dose escalation. Response assessment is completed every 2 cycles (starting with cycle 3) and per RECIST 1.1. Correlative studies will explore associations between tumour response and baseline mutational and met amplification status. To date 14 (experimental) and 6 (exploratory) pts have been enrolled. Median age is 64 (range 51-80). All pts have received chemotherapy and 70% prior radiation. 44 cycles have been completed (median 2 range 1-5). Once the final pts have been accrued to the experimental arm, a decision to proceed to stage II will be made. Clinical trial information: NCT01935934.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".