Phase II study of MKC-1 in patients with metastatic or resistant epithelial ovarian cancer or advanced endometrial cancer
Bibliographic record
Abstract
5577 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity in xenograft models of human ovarian and endometrial cancers. MKC-1 also reduces pAKT, an attractive target in endometrial cancer due to frequent PTEN mutations. Methods: The objective of this phase II study is to assess the efficacy of MKC-1 in 2 patient (pt) populations: metastatic or recurrent platinum-resistant ovarian cancer (EOC) and advanced endometrial cancer (EC). Three prior lines of treatment were allowed in both groups. A two arm, parallel group multicenter 2-stage design was used. The primary endpoint was tumor response by RECIST or CA-125. MKC-1 125 mg/m2 was administered orally twice daily for 14 days in 28-day cycles. Results: Accrual to stage one is complete with 21 pts in each arm. 19 pts with EOC (median age 56 yrs, range 31–71) and 9 patients with EC (median 63 range 50–74) were available for efficacy. A total of 66 cycles (EOC/EC: 39/27cycles) median 2 per patient (range 1–8) were delivered. 11/4 pts had prior adjuvant CT, 14/10 had prior systemic CT for advanced disease, and 2/6 received prior radiation. In pts with EOC, 7 pts have stable disease (SD), 12 progressive disease (PD), 2 remain on study. Median time to progression is 1.8 months. In pts with EC 4 pts had SD, 5 PD, 6 remain on study. Toxicity data are available in 28 pts (17/11). Most common adverse events (AE) possibly related to MKC-1 were fatigue, nausea, elevated ALT or AST, urine discoloration, anemia, anorexia, elevated AP and gastrointestinal disorder in 55%, 39%, 36%, 24%, 23%, 21%, 21%, and 21 % of cycles respectively. The only possibly related grade 3+ AEs were neutropenia, leucopenia and hyponatremia in 9 %, 3 %, and 2% of cycles. Conclusions: MKC-1 was well tolerated in both patient populations. Single agent MKC-1 has insufficient activity in platinum resistant EOC to warrant further investigation. Updated clinical data for both patient groups will be presented at the meeting. [Table: see text]
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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) | 0.003 | 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".