A multi center, phase 2 study to Evaluate safety and efficacy of total Neoadjuvant treatment of long courSE radiotherapy followed by cheMotherapy, capecitaBine combined with oxaliplatin (CAPOX) for Locally advanced rEctal cancer(ENSEMBLE-2)

JRCT ID: jRCTs071210143

Registered date:30/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Rectal cancer
• Date of first enrollment: 06/05/2022
• Target sample size: 27
• Study type: Interventional

Intervention(s)

(1)Neoadjuvant chemoradiation therapy: 1.8Gyx28, Capecitabine 1600mg/m^2/day
(2)Neoadjuvant chemotherapy: CAPOX (Oxaliplatin 130mg/m^2, Capecitabine2000mg/m^2/day, d1-14, 3week)x4cycles
(3)Operation: Total mesorectum excision with radical lymph node dissection

Outcome(s)

• Primary Outcome: Pathological complete response: pCR

Secondary Outcome

Clinical complete response (cCR) rate: The state of the disappearance on the image is defined as cCR.
Radical resection rate.
Recurrence form
Relapse-free survival (RFS)
Overall survival (OS)
Protocol treatment completion rate
Completion rate of neoadjuvant chemoradiation therapy
Completion rate of neoadjuvant chemotherapy
Safety
1.Neoadjuvant treatment related adverse event rate judged by CTCAE ver5.0
2.Intraoperative safety evaluation judged by CTCAE ver5.0
3.Postoperative safety evaluation judged by CTCAE ver5.0 and Clavien-Dindo classification

Key inclusion & exclusion criteria

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

Include criteria

(1)Written informed consent obtained from every patient before enrollment in the study.
(2)Patients with rectal adenocarcinoma confirmed by histological examination.
(3)Radical resection is clinically possible without findings of any distant metastases.
(4)Aged >=20 years.
(5)Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
(6)The lower edge of the tumor is within 12cm of the anal margin (AV).
(7)No prior treatment for the tumor.
(8)There is no history of radiation therapy to the pelvic area, including the treatment for other types of cancer.
(9)Rectal cancer cases with cT3-T4N0M0 or TanyN+M0 at the pretreatment diagnosis.
(10)The following criteria should be met for the major organ functions within 14 days before the registration. If there are multiple test results within the relevant period, the one most recent result to the registration will be adopted. The blood transfusion and hematopoietic factor preparations will not be administered within 14 days before the test.
a.Neutrophil count>=1,500 cells/mm^3
b.Platelet count>=100,000 cells/mm^3
c.Hemoglobin>=9.0 g/dL
d.Total bilirubin<=2.25 mg/dL
e.AST (GOT)<=100 IU/L
f.ALT (GPT)<=100 IU/L
g.ALP (IFCC)<=283 IU/L
h.Creatinine <1.5 mg/dL Creatinine clearance (CCr)>=45 mL/min

Exclude criteria

(1)Patients who received treatment by any of the following within a certain period before the start of the protocol treatment.Extensive surgery within 4 weeks (stoma construction or CV port construction will be excluded).
(2)Cases with T4b, levator ani muscle invasion or lateral lymph node positive.
(3)Patients with severe pulmonary disease, including interstitial pneumonia, pulmonary fibrosis and severe emphysema.
(4)Patients underwent stent to stenosis lesion.
(5)Patients with severe comorbidities (heart failure, renal failure, liver failure, hemorrhagic digestive ulcer, intestinal paralysis, intestinal obstruction, uncontrolled diabetes, etc.)
(6)Patients with active multiple cancers. Synchronous double cancer and metachronous double cancer within a disease-free interval of 5 years. Lesions consistent with carcinoma in situ or intramucosal carcinoma that have been cured by local treatment are not classified as active multiple cancers.
(7)Pregnant women, lactating woman, positive pregnancy tests, or no intention of contraception.
(8)Patients with HBsAg or HCVAb positive.
(9)Patients with HIV infection.
(10)Patients whom a lead investigator or primary physician deems are not appropriate for this study.

Related Information

• Primary Sponsor: KAGAWA Yoshinori