JCOG2010: Single-arm confirmatory trial of the total neoadjuvant therapy and watch and wait strategy for the patients with low rectal cancer Total Neoadjuvant Therapy and Watch and Wait strategy for Low Rectal Cancer

JRCT ID: jRCTs031220288

Registered date:24/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Rectal cancer
• Date of first enrollment: 02/09/2022
• Target sample size: 105
• Study type: Interventional

Intervention(s)

(1) Chemoradiotherapy:
Capecitabine 1,650 mg/m2/day twice daily after breakfast and dinner for 5 days, followed by 2 days off for 6 weeks.
Radiation (45 Gy/25 whole pelvis + primary tumor boost 5.4 Gy/3 times).
(2) Consolidation chemotherapy: 4 courses of CAPOX therapy
Oxaliplatin (130 mg/m2) day 1 + capecitabine (2,000 mg/m2/day twice daily) for 14 consecutive days, up to 4cycles.
(3) Watch & Wait strategy
Response evaluation is assessed after (1) and (2) therapy.
If the evaluation is clinical complete response (cCR), follow-up is performed for 5 years after (2) therapy or until tumor progression.
If the evaluation is nearCR, response evaluation is continued.
If the evaluation is Incomplete Response, radical resection is performed.
(4) Radical resection
Total mesorectal excision (TME) or tumor-specific mesorectal excision (TSME) is performed.

Outcome(s)

Primary Outcome

Phase II : cCR rate at final response evaluation
Phase III : Overall survival

Secondary Outcome

Phase II part: cCR+nearCR rate at final response evaluation, rectal preservation rate (W&W strategy + local therapy patients), adverse event rate (chemoradiation, consolidation chemotherapy), surgical complication rate, concordance rate between central and each facility in efficacy assessment
Phase III part: Progression-free survival, local progression-free survival, rectal preservation survival, 5-year no-stoma survival rate, cCR rate at final response evaluation, cCR + nearCR rate at final response evaluation, concordance rate between central and each facility for efficacy, local regrowth rate of W&W strategy cases, rectal sparing rate (W&W strategy + local resection patients), R0 resection rate in radical surgery cases, adverse event rate (chemoradiotherapy, consolidation chemotherapy), surgical complication rate,
anorectal defecation function score (Wexner score), urinary drainage score (I-PSS), sexual function score (IIEF5)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

(1) Endoscopic biopsy from a primary rectal lesion has been histologically diagnosed as tubular adenocarcinoma (well or moderately differentiated). Or endoscopic biopsy from a primary lesion in the anal canal has been histologically diagnosed as adenocarcinoma (rectal type) and further diagnosed as well differentiated or moderately differentiated.
(2) The tumor is predominantly located in the upper rectum (Ra), lower rectum (Rb), or anal canal (P).
(3) The lower margin of the tumor is located between the perineal reflection and the anal verge (Rb-P).
(4) Comprehensive diagnosis of cT2-cT3 by abdominal and pelvic contrast CT* and pelvic contrast MRI* with a slice thickness of 5 mm or less. (JSCCR guideline, 9th Edition)
*Contrast-enhanced CT or contrast-enhanced MRI are preferred, but plain CT or plain MRI is acceptable, respectively.
(5) No lymph node satisfying either 1. or 2. below is present on comprehensive diagnosis by contrast-enhanced CT* of the chest, abdomen, and pelvic region with a slice thickness of 5 mm or less and contrast-enhanced MRI* of the pelvic region.
1. 10 mm or more in short diameter
2. 7 mm or more in short diameter and one or more of the following (a)-(c)
(a) irregular margins
(b) MRI shows internal inhomogeneous low-signal areas
(c) Circular (long to short diameter ratio < 1.5)
(6) No distant metastasis.
(7) The maximum diameter of the tumor is less than 5 cm on comprehensive diagnosis by contrast-enhanced CT* of the abdomen and pelvis with a slice thickness of 5 mm or less, contrast-enhanced MRI *of the pelvis, and endoscopy of the lower gastrointestinal tract.
(8) Comprehensive diagnosis using colonoscopy and imaging studies (barium enema or abdominal/pelvic contrast CT* or CT colonography) does not reveal multiple carcinomas. However, cTis and cT1a (cancer is expected to remain in the submucosal layer and invade less than 1,000 micrometre) lesions that are expected to be curatively resectable by endoscopic resection are not considered multiple carcinomas.
(9) Patients must be between 18 and 75 years of age on the date of enrollment.
(10)Performance status (PS) is 0 or 1 according to ECOG criteria
(11) The patient does not wish to undergo surgical resection, the standard of care, as initial treatment, but wishes to undergo salvage treatment, including surgical resection, in the event of residual or recurrent disease.
(12) The patient is able to take oral intake.
(13)The patient has not undergone rectal resection (except for endoscopic resection), radiation therapy to the pelvic region, or any previous treatment, including treatment for other types of cancer.
(14)The most recent laboratory values within 14 days prior to enrollment (the same day of the week two weeks prior to the date of enrollment is acceptable) meet all of the following
1. neutrophil count >= 1,500/mm3
2. Hemoglobin >= 9.0 g/dL (no blood transfusion within 14 days prior to the date of blood collection for the test used for registration)
3. Platelet count >=100,000/mm3
4. Total bilirubin <= 2.0 mg/dL
5. AST<=100 U/L
6. ALT<=100 U/L
7. Serum creatinine <= 1.5 mg/dL
(15) Written consent to participate in the study has been obtained from the patient.

Exclude criteria

(1) Active multiple cancers (simultaneous multiple cancers and multiple cancers with a disease-free interval of 5 years or less. However, multiple cancers do not include stage I prostate cancer, stage 0 or stage I laryngeal cancer that has had a complete response to radiotherapy, or cancer that has been completely resected with a 5-year relative survival rate equivalent to 95% or greater).
(2) Infectious diseases requiring systemic treatment.
(3) Have a fever of 38.0 degrees Celsius or higher at the time of registration.
(4) Pregnant, possibly pregnant, within 28 days postpartum, or lactating. Males whose partners wish to become pregnant.
(5) Patients with psychiatric disorders or psychiatric symptoms that interfere with daily life and make it difficult for them to participate in the study.
(6) Receiving continuous systemic administration (oral or intravenous) of steroids or other immunosuppressive drugs.
(7) Complicated with poorly controlled diabetes mellitus.
(8) Patient has uncontrolled hypertension.
(9) Complicated with unstable angina (angina with onset or worsening within the last 3 weeks) or a history of myocardial infarction within the last 6 months.
(10) Poorly controlled valvular heart disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy.
(11) HBs antigen positive.
(12) HIV antibody positive.
(13)Has one or more of the following complications diagnosed by chest CT: interstitial pneumonia, pulmonary fibrosis, or severe emphysema.

Related Information

• Primary Sponsor: KANEMITSU Yukihide
• Source(s) of Monetary Support: National Cancer Center Japan