NCIC CTG IND.206: A phase II umbrella trial of sunitinib (S) or temsirolimus (T) in advanced rare cancers.
Bibliographic record
Abstract
2594 Background: Patients (Pts) with rare cancers have few treatment options due to the challenges of conducting clinical trials when projected accrual is low. However, rare cancers may have driver mutations that can be targeted with potentially dramatic therapeutic effects. Methods: IND.206 is a multi-center, non-randomized phase II study of S or T in 11 rare tumor cohorts ( < 100 eligible patients/year in Canada). Cohorts: 8 histologic, 2 genetic, 1 exploratory unspecified. Pts received S (50 mg PO daily x 28 days, q 6 weeks) or T (25 mg IV weekly, q 6 weeks). Each cohort and drug was evaluated separately using a 2 stage design targeting 5 versus 25% RECIST response rate. Blood and tumor were collected for genomic analyses. For trial efficiency, 1) pts could be re-entered to the alternate drug at progression; 2) data collection and SAE reporting were streamlined; 3) cohorts could be stopped early for activity, inactivity or failure to accrue. Central pathology review was performed. Results: The trial was activated in 7/2011. To date, 134 patients were enrolled, 156 registered (22 pts crossed over). 132 are evaluable for response, 134 are evaluable for toxicity. 4 cohorts failed meet the minimum accrual. Only the medullary thyroid cohort treated with S met the protocol defined activity level. Responses were seen in the following: medullary thyroid carcinoma (7/16 on S), clear cell carcinomas of ovary/endometrium (3/22 S; 3/22 T), pheochromocytomas and paragangliomas (1/4 S), 1 extraskeletal myxoid chondrosarcoma (ESMCS) on S, 1 perivascular epithelioid cell tumor on T. Responses were not seen in vascular sarcomas (n = 16 10 S, 6 T) Ewing’s sarcoma family tumours (n = 10, T), adrenocortical (n = 12 S, 10 T) or thymic carcinomas (n = 5 S, 2 T) despite case reports in the literature. Toxicity was consistent with previously studies although quantity of grade 1-2 and expedited reports were reduced as per protocol. Genomic studies are underway. Conclusions: S and T induce responses in clear cell carcinomas of ovary and endometrium, medullary carcinoma of thyroid, paraganglioma and ESMCS. Case reports in the literature may overestimate activity. Our umbrella design is efficient for evaluating drug activity in rare cancers. Clinical trial information: NCT01396408.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.008 | 0.002 |
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".