N-of-1 Trial: Actionable Target Identification in Metastatic Cancer for Palliative Systemic Therapy
Summary
The metastatic lesions may be very different from the primary tumor because of intrinsic tumor heterogenity, clonal selection through metastatic process and following previous cytotoxic treatments. Metastatic tumor harboring actionable targets or signaling pathways may respond to inhibitory agents directed against specific aberrations irrespective of tumor origin. In the MetAction study, patients will receive therapy based on molecular aberrations in the metastatic lesions, actionable target identification (ATI), rather than on histological tumor type. The ATI rate in an unselected metastatic patient population is uncertain, and response rates associated with ATI based targeted therapy have hardly been reported. In this perspective, The MetAction study is essentially a feasibility study aiming to tailor metastatic cancer therapy based on genomic profiles.
Timeline
- Start
- 2014-05
- Primary completion
- 2018-08
- Completion
- 2018-08
Outcome
Met primary endpoint
paper Among 10 patients who received treatment until radiologic evaluation, 6 (46% of the eligible cases) met the primary endpoint. PMID 32208873 ↗
Publications
- Ree AH, Maelandsmo GM, Flatmark K, Russnes HG, Gomez Castaneda M, Aas E. Cost-effectiveness of molecularly matched off-label therapies for end-stage cancer - the MetAction precision medicine study. Acta Oncol. 2022 Aug;61(8):955-962. doi: 10.1080/0284186X.2022.2098053. Epub 2022 Aug 9.
- Ree AH, Nygaard V, Boye K, Heinrich D, Dueland S, Bergheim IR, Johansen C, Beiske K, Negard A, Lund-Iversen M, Nygaard V, Hovig E, Nakken S, Nasser S, Julsrud L, Reisse CH, Ruud EA, Kristensen VN, Florenes VA, Geitvik GA, Lingjaerde OC, Borresen-Dale AL, Russnes HG, Maelandsmo GM, Flatmark K. Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study. Acta Oncol. 2020 Jul;59(7):733-740. doi: 10.1080/0284186X.2020.1742377. Epub 2020 Mar 25.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Afatinib | Small molecule | — | — |
| Subject | Cetuximab | Monoclonal antibody | — | — |
| Subject | Crizotinib | Small molecule | — | — |
| Subject | Dabrafenib | Small molecule | — | — |
| Subject | Erlotinib | Small molecule | — | — |
| Subject | Everolimus | Small molecule | — | — |
| Subject | Gefitinib | Small molecule | — | — |
| Subject | Imatinib | Small molecule | — | — |
| Subject | Lapatinib | Small molecule | — | — |
| Subject | Nilotinib | Small molecule | — | — |
| Subject | Panitumumab | Monoclonal antibody | — | — |
| Subject | Ruxolitinib | Small molecule | — | — |
| Subject | Sunitinib | Small molecule | — | — |
| Subject | Temsirolimus | Small molecule | — | — |
| Subject | Trastuzumab | Monoclonal antibody | — | — |
| Subject | Vandetanib | Small molecule | — | — |
| Subject | Vemurafenib | Small molecule | — | — |
| Subject | dasatinib anhydrous | Small molecule | — | — |