NOMINATE trial

JRCT ID: jRCTs051200121

Registered date:28/01/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: rectal cancer
• Date of first enrollment: 29/03/2021
• Target sample size: 224
• Study type: Interventional

Intervention(s)

arm A:Preoperative CRT(28*1.8 Gy+Capecitabine 825mg/m2 bid, day 1-5, 8-12, 15-19, 22-26, 29-33, 36-38)+consolidation chemotherapy(CapeOX 6 courses: Capecitabine 2000mg/m2/day, d1-14, Oxaliplatin 130mg/m2, day1, Q3w)+TME or non-operative management for cCR/near-cCR
arm B:Induction chemotherapy(CapeOX+Bevacizumab 3 courses:Capecitabine 2000mg/m2/day, d1-14, Oxaliplatin 130mg/m2, day1, Bevacizumab 7.5mg/kg, day 1, Q3w)+Preoperative CRT(28*1.8 Gy+Capecitabine 825mg/m2 bid, day 1-5, 8-12, 15-19, 22-26, 29-33, 36-38)+consolidation chemotherapy(CapeOX 3 courses)+TME or non-operative management for cCR/near-cCR

Outcome(s)

• Primary Outcome: Rate of pCR and cCR >= 2 years

Secondary Outcome

Clinical complete response rate, Near-clinical complete response rate, Rate of non-operative management, Overall survival, Distant metastasis-free survival, Locoregional failure-free survival,
Time to disease-related treatment failure, TME-free survival, Permanent stoma-free survival,
Safety of the treatment, Completion rate of the treatment, Fecal incontinence according to Wexner Score and LARS-scale, Quality of life according to EORTC Quality of Life questionnaire - C30 and CR29,
TME cases- Surgical morbidity, R0 resection rate, Pathological stage, Dworak tumor regression grade
NOM cases- Local regrowth rate, Time to local regrowth, Salvage surgery rate in patients with local regrowth, Surgical morbidity in salvage surgery, R0 resection rate in salvage surgery

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histologically confirmed diagnosis of adenocarcinoma of the rectum
2) <= 5 cm from the anal verge or candidate for APR or intersphincteric resection prior to neoadjuvant therapy according to the primary surgeon
3) Clinical stage II (cT3-4N0) or stage III (cT3-4N1-3) by MRI and CT (cohort1)
Clinical stage cT2NanyM0 by MRI and CT (cohort2)
4) ECOG PS 0 or 1
5) Age >= 20 years
6) Adequate organ functions within 28 days prior to entry
i. Neutrophils >= 1,500 /mm3
ii. Platelets >= 10*104 /mm3
iii. Hemoglobin >= 9.0 g/dL
iv. Total bilirubin <= 2.0 mg/dL
v. AST, ALT <= 100 IU/L
vi. Serum creatinine <= 1.5 mg/dL or Ccr >= 60 mL/min/body
vii. Urine protein/creatinine < 1
7) If there is bowel obstruction or strong stricture, stoma construction prior to neoadjuvant therapy
8) Written informed consent

Exclude criteria

1) Patients with a history of a prior malignancy within the past 5 years, except for adequately treated cancer with 5-year relative survival rate >= 95%
2) History of pelvic irradiation
3) Administration contraindication of capecitabine, oxaliplatin, or bevacizumab
4) Uncontrolled active infection
5) Fever 38.0 >= degree celsius at entry
6) Possible pregnant or pregnant or nursing female
7) Patients with concurrent psychiatric condition or disease which would make them inappropriate candidates for entry into this study in the investigator's judgement
8) Patients with concurrent serious complication (heart failure, interstitial lung disease or pulmonary fibrosis, uncontrolled diabetes, renal failure, liver failure, hypertension, thrombotic disease, gastrointestinal fistula, etc)
9) History of operation <= 4 weeks or minor operation such as stoma construction <= 2 weeks
10) Deficient mismatch repair (dMMR) determined by immunohistochemistry and/or MSI testing using pre-treatment biopsy specimens
11) Other conditions not suitable for this study in the investigator's judgement

Related Information

• Primary Sponsor: Akiyoshi Takashi