Table 1.
Phase 2 and 3 randomized clinical trials evaluating targeted molecular pathways associated with colorectal cancer SCs.
| Trial | Pathway | Phase | CRC Patients | Intervention | Comparator | Significant Results | Reference |
|---|---|---|---|---|---|---|---|
| CORRECT | Wnt/β-Catenin | 3 | Pretreated | Regorafenib | Placebo | Regorafenib mOS, 6.4 months. Placebo 5 m. HR 0.77; one-sided p = 0.0052 | [18] |
| COAST | Wnt/β-Catenin | 3 | Following curative resection of liver metastases after completion of planned chemotherapy | Regorafenib | Placebo | Only 25 patients randomized. SAEs were observed in 14.29% with regorafenib | [24] |
| NCT01830621 | JAK/STAT | 3 | Pretreated | Napabucasin | Placebo | OS did not significantly differ. In pSTAT3-positive patients, napabucasin showed longer survival: median 5.1 months (95% CI 4.0–7.5; HR 0.41, 0.23–0.73, p = 0.0025) | [89] |
| LYNK-003 | DNA Damage Response | 3 | Advanced CRC patients who had not progressed on first-line FOLFOX plus bevacizumab | Olaparib/ Olaparib plus bevacizumab |
5-FU + bevacizumab | The study was terminated for futility after enrolling 309 patients | [109] |
| NCT00985192 | PI3K/Akt/mTOR | 2 | Pretreated | Sonolisib (PX-866) and cetuximab | Cetuximab | No PFS superiority. The treatment-related toxicity was higher in the combination arm | [61] |
| NCT02278133 | PI3K/Akt/mTOR | 2 | BRAF V600E-mutated mCRC | Alpelisib, encorafenib, and cetuximab | Encorafenib and cetuximab | The combination of cetuximab, encorafenib, and alpelisib resulted in a median PFS 5.4 months (HR 0.69; p = 0.064). ORR 27% in 52 patients | [67] |
| NCT01490996 | NF-κB | 2a | Pretreated | Curcumin + FOLFOX | FOLFOX | No statistically significant differences in PFS (HR 0.57; p = 0.2). However, there was a significant difference in OS in the ITT population (HR 0.339; p = 0.016) | [79] |
| NCT02119676 | JAK/STAT | 2 | Pretreated | Ruxolitinib + regorafenib | Regorafenib | The combination did not improve OS or PFS | [93] |
| NCT02305758 | DNA Damage Response | 2 | Pretreated | Veliparib + FOLFIRI | Placebo + FOLFIRI | No significant differences in PFS or OS. The veliparib group had significantly higher frequencies of anemia and neutropenia | [105] |
| NCT00636610 | Hedgehog | 2 | Pretreated | Vismodegib + FOLFOX/FOLFIRI + bevacizumab | Placebo + FOLFOX/ FOLFIRI + bevacizumab | The overall response rates for placebo-treated and vismodegib-treated patients were 51% (90% CI: 43–60) and 46% (90% CI: 37–55), respectively | [32] |