A Phase 2 Study of Amrubicin in Relapsed or Refractory Thymic Malignancies
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Other
|Official Title:||A Phase II Study of Amrubicin in Relapsed or Refractory Thymic Malignancies|
- Overall Response Rate (ORR) [ Time Frame: 2 years ]
Tumor response rate was assessed radiographically by the Response Evaluation Criteria In Solid Tumors (RECIST), and the overall response rate (ORR) was expressed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate (ie, CR + PR).
RECIST criteria define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. RECIST criteria offer a simplified and conservative extraction of imaging data suitable for wide application in clinical trials. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories:
- Complete response (CR) = Disappearance of all target lesions
- Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions
- Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions
- Stable disease (SD) = Small changes that do not meet above criteria
- Median Progression-free Survival (PFS) [ Time Frame: 2 years ]Median Progression-free survival in patients with thymic malignancies treated with amrubicin
- Disease Control Rate (DCR) [ Time Frame: 2 years ]
Disease control rate (DCR) is the sum of Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate , and is expressed here as the sum of the Overall Response Rate (ORR = CR + PR) plus the Stable Disease (SD) rate, ORR + SD.
Response was assessed by the RECIST criteria, elaborated above.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||December 2017|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks
35 mg/m2; IV on days 1-3 each 3 week cycle
Other Name: Calsed
Amrubicin, a synthetic 9-aminoanthracycline, is structurally similar to doxorubicin, but has a different primary mode of action. It acts primarily as an inhibitor of DNA topoisomerase II, exerting its cytotoxic effects by stabilizing a topoisomerase II mediated cleavable complex. This inhibition is significantly more than that seen in doxorubicin, which, in contrast, tends to demonstrate more DNA intercalation than amrubicin.
It has not yet been evaluated for use in thymic malignancies, but given its efficacy in NSCLC and small cell lung cancer (SCLC), as well as the known efficacy of other anthracyclines and topoisomerase II inhibitors in first-line thymoma treatment, it warrants study for use in the second line and beyond in refractory or relapsed patients. Unlike doxorubicin, amrubicin has had minimal cardiotoxicity even with ongoing use, which also makes it a promising agent for use in the second line even for patients who have previously been exposed to, and potentially helped by, doxorubicin.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01364727
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Heather A. Wakelee||Stanford University|