Table 3.
Ongoing trials investigating the TNT approach and organ preservation
| TNT type | Trial | Design | N | Arms | 1° endpoint | 2° endpoint |
|---|---|---|---|---|---|---|
| Consolidation | RAPIDO trial53 (NCT01558921) | Phase III RCT | 842 | Standard long course CRT → surgery → optional adjuvant CAPOX (8×) | 3‐y DFS | Toxicity, R0 resection rate, pCR QOL, functional outcome OS |
| SC‐RT (5 Gy × 5) → CAPOX (6×) → surgery | ||||||
| Consolidation | TRIGGER trial70 (NCT02704520) | Phase III RCT | 633 | Refer to Figure 2 | Rate of patient recruitment and randomization | Rate of unit recruitment, toxicity, reproducibility of mrTRG reporting, surgical morbidity, pCR, residual tumor density, surgical quality rates |
| Consolidation or induction | Smith et al71 (NCT02008656) | Phase II RCT | 202 | Induction CTx+CRT | 3‐y RFS | Organ preservation rate, compliance, toxicity, functional outcome, QOL |
| CRT+consolidation CTx | ||||||
| Consolidation | KONCLUDE76 (NCT02843191) | Phase III RCT | 358 | Standard CRT→ surgery → mFOLFOX6 (8×) | pCR 3‐y DFS | Toxicity, R0 resection rate, tumor response rate, postoperative morbidity, peripheral neuropathy at 3 y after surgery |
| Standard CRT → mFOLFOX6 (3×) → surgery → mFOLFOX (5×) | ||||||
| TNT without RT | PROSPECT75 (NCT01515787) | Phase III RCT | 1060 | 5‐FU +CRT → surgery → FOLFOX (8×) | R0 rate DFS LRR | pCR OS Toxicity Rate of CRT |
| FOLFOX (6×) → tumor response assessment → TME or CRT Adjuvant therapy if R0 → FOLFOX (6×) R1+ → FOLFOX (4×)+CRT | ||||||
| TNT without RT | BACCHUS77 (NCT01650428) | Phase II RCT | 60 | FOLFOX + bev | pCR rate | Response rate CRM negative resection T and N downstaging PFS, DFS, OS, LRR 1‐y colostomy rate Toxicity, compliance |
| FOLFOXIRI + bev | ||||||
| TNT with or without RT | FOWARC78 (NCT01211210) | Phase II RCT | 495 | Standard CRT | 3‐y DFS | pCR, R0, LRR, OS Predictive biomarkers QOL, toxicity |
| FOLFOX + CRT | ||||||
| FOLFOX alone |
5‐FU, 5‐fluorouracil; bev, bevacizumab; Cape, capecitabine; CAPOX, capecitabine/oxaliplatin; CRM, circumferential resection margin; CRT, chemoradiotherapy; CTx, chemotherapy; DFS, disease‐free survival; FOLFOXIRI, oxaliplatin/5‐FU/irinotecan; Gy, gray; LRR, local recurrence rate; mFOLFOX6, 5‐fluorouracil, leucovorin, and oxaliplatin; mrTRG, magnetic resonance imaging‐derived tumor regression grading system; OS, overall survival; pCR, pathological complete response; PFS, progression‐free survival; QOL, quality of life; R0, microscopically clear resection; RCT, randomized controlled trial; RT, radiotherapy; SC‐RT, short‐course radiotherapy; TME, total mesorectal excision; TNT, total neoadjuvant therapy.