A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies
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Matthew A Gubens1, Matthew Burns2, Susan M Perkins2
1University of California, San Francisco, CA, United States.
Objectives:
Thymic malignancies are rare, and options are limited for metastatic disease. Src plays a role in normal thymic epithelial maturation, and its inhibition with the oral compound saracatinib was postulated to be effective in controlling thymic malignancy.
Materials And Methods:
Patients with unresectable thymic malignancy were treated with saracatinib 175mg by mouth daily in 28 days cycles with radiographic evaluation at cycle 2 day 1 for safety, then cycle 3 day 1 and every 8 weeks thereafter. Response was evaluated by RECIST 1.0. A two-stage optimal design was used, powered to detect a true response rate of 20%.
Results:
21 patients were enrolled at two institutions, 12 of them with thymoma, 9 with thymic carcinoma. Thymoma patients received a median of 4.5 cycles and thymic carcinoma patients a median of 1 cycle. There were no responses, so accrual was halted after the first stage per protocol. 9 patients had stable disease beyond the first assessment. Median time to progression was 5.7 months for thymoma patients and 3.6 months for thymic carcinoma patients. Saracatinib was well tolerated.
Conclusion:
Src inhibition by saracatinib did not produce any radiographic responses, though some patients did experience stable disease. Though negative, this study shows the feasibility of completing a trial in this rare disease, and of accruing reasonably significant numbers of thymic carcinoma patients. More clinical trials are required for this population (NCT00718809).
Insights
Src inhibition with saracatinib did not yield responses in thymic malignancies. While well-tolerated, the study highlights challenges and the need for further clinical trials in this rare cancer.
Area of Science:
- Oncology
- Pharmacology
- Rare Cancers
Background:
- Thymic malignancies are rare with limited treatment options for advanced disease.
- Src kinase is implicated in thymic epithelial cell maturation.
- Saracatinib, an oral Src inhibitor, was investigated for potential efficacy.
Purpose of the Study:
- To evaluate the efficacy of saracatinib in patients with unresectable thymic malignancy.
- To assess the safety and tolerability of saracatinib in this patient population.
Main Methods:
- A two-stage optimal design clinical trial was conducted.
- 21 patients with thymoma or thymic carcinoma received saracatinib 175mg daily.
- Radiographic response was assessed using RECIST 1.0 criteria.
Main Results:
- No objective radiographic responses were observed in any patients.
- 9 patients achieved stable disease; median time to progression was 5.7 months (thymoma) and 3.6 months (thymic carcinoma).
- Saracatinib was generally well-tolerated.
Conclusions:
- Src inhibition with saracatinib did not demonstrate radiographic response in thymic malignancies.
- The study confirmed the feasibility of conducting clinical trials for rare thymic cancers.
- Further clinical trials are warranted for this patient group.
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