Phase I/II study of alectinib in lung cancer with RET fusion gene: study protocol
Shinji Takeuchi1, Toshinori Murayama2,3, Kenichi Yoshimura2
1Division of Medical Oncology, Cancer Research Institute, Kanazawa University.
Background:
The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC.
Methods/Design:
RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design. The primary endpoint is safety. In step 2, alectinib will be administered at the recommended dose (RD) defined by step 1. The primary endpoint is the response rate of RET inhibitor treatment-naïve patients.
Conclusion:
This is the first study to investigate the safety and preliminary efficacy of alectinib in RET fusion-positive NSCLC patients. If successful, alectinib treatment may lead to substantial and important changes in the management of NSCLC with RET fusion genes. J. Med. Invest. 64: 317-320, August, 2017.
Insights
This study explores alectinib for non-small cell lung cancer (NSCLC) with rearranged during transfection (RET) fusions. It assesses safety and efficacy, potentially changing treatment for this NSCLC subtype.
Area of Science:
- Oncology
- Pharmacology
Background:
- Rearranged during transfection (RET) fusion gene is an oncogene in 1-2% of non-small cell lung cancers (NSCLCs).
- Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, shows potential efficacy in RET fusion-positive NSCLC.
Purpose of the Study:
- To investigate the safety and preliminary efficacy of alectinib in patients with RET fusion-positive NSCLC.
- To determine the recommended dose of alectinib for further studies.
Main Methods:
- Phase 1/2 study design.
- Step 1: Dose escalation of alectinib (600 or 450 mg twice daily) using a 3+3 design to assess safety.
- Step 2: Evaluate the response rate of alectinib at the recommended dose in treatment-naïve patients.
Main Results:
- Primary endpoint for Step 1 is safety.
- Primary endpoint for Step 2 is response rate in treatment-naïve patients.
Conclusions:
- This is the first study evaluating alectinib for RET fusion-positive NSCLC.
- Successful outcomes could significantly alter NSCLC management for patients with RET fusion genes.
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