Clinical trial NCT04288999: Surgery Plus Chemo Versus Chemoradiotherapy Followed by Surgery Plus Chemo for Locally Recurrent Rectal Cancer
Official title: JCOG1801: A Phase III Randomized Controlled Trial Comparing Surgery Plus Adjuvant Chemotherapy With Preoperative Chemoradiotherapy Followed by Surgery Plus Adjuvant Chemotherapy for Locally Recurrent Rectal Cancer (RC-SURVIVE Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer Recurrent
Keywords: Rectal cancer
Locally recurrent rectal cancer
Chemoradiotherapy
Surgery
Chemotherapy
Lead sponsor: National Cancer Center Hospital East
Sponsor class: OTHER
Collaborators: name: Japan Clinical Oncology Group
name: Japan Agency for Medical Research and Development
First posted: 2020-02-28
Enrollment: 110
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: JCOG1801 is a randomized phase III trial which was initiated in Japan in August 2019 to confirm the superiority of preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for local relapse-free survival over standard treatment, i.e. surgery plus adjuvant chemotherapy, for previously non-irradiated locally recurrent rectal cancer.

Detailed description: In all, 110 patients from 43 Japanese institutions will be recruited over a period of 6 years. Eligible patients would be registered and randomly assigned to each group with an allocation ratio of 1:1. The primary endpoint is local relapse-free survival. The secondary endpoints are overall survival, relapse-free survival, proportion of local relapse, proportion of distant relapse, proportion of patients with pathological R0 resection, response rate of preoperative chemoradiotherapy (preoperative chemoradiotherapy arm), pathological complete response rate (preoperative chemoradiotherapy arm), proportion of patients who completed the protocol treatment, incidence of adverse events (adverse reactions), and quality of life after surgery.

Eligibility criteria: Inclusion Criteria:

1. Histopathologically proven adenocarcinoma or adenosquamous carcinoma on the resected specimen of the initial rectal cancer or endoscopic biopsy from the initial rectal cancer.
2. The main tumor location of the initial rectal cancer is upper, middle or lower rectum, or anal canal.
3. Either of the following treatments was performed for the initial rectal cancer, and classified as R0/1 or ER (Endoscopical R)0/1 on pathological diagnosis.

   i) Surgical resection (including local resection, with or without lymph node dissection).

   ii) Endoscopic resection.
4. Patients with distant metastasis during or after treatment for the initial rectal cancer, and radical surgical resection or radical radiotherapy performed more than 168 days before registration is eligible.
5. Recurrent rectal cancer diagnosed by any of the following modalities after treatment for the initial rectal cancer.

   i) The recurrent lesion is pathologically diagnosed. ii) Diagnosed as local recurrence by more than two modalities among contrast-enhanced CT, contrast-enhanced MRI, or positron emission computed tomography (PET).

   iii) Chronological progression of the lesion seen on more than one modality among contrast-enhanced CT, MRI, or PET.
6. The main tumor location is within pelvis as seen on contrast-enhanced CT and MRI if recurrent lesion is multiple, or recurrent lesions spread outside of pelvis continuously.
7. LRRC is diagnosed with no following condition. i) Judged as resectable endoscopically. ii) Depth of invasion within the muscularis propria as seen on contrast-enhanced CT, MRI, or PET in case of recurrence inside the intestine iii) Solitary ovarian metastasis. iv) Recurrence of the common iliac lymph node alone.
8. LRRC is diagnosed as resectable, and all the following conditions must be fulfilled:

   i) No distant metastasis on contrast-enhanced CT (cM0). ii) Estimated circumferential resection margin \>0 mm. iii) Leg amputation not required. iv) Preservation of the first sacral nerve possible.
9. No prior surgery for recurrent rectal cancer.
10. No prior pelvic irradiation for any malignancies.
11. A patient who has received systemic chemotherapy for any malignancies and the final dose was administered more than 14 days ago.
12. Age at registration is 20 to 80 years old.
13. Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1.
14. Measurable lesion is not mandatory.
15. Adequate oral intake.
16. Sufficient organ function. i) Neutrophil count \>= 1,500/mm3 ii) Hemoglobin \>= 9.0 g/dL iii) Platelet count \>= 100,000/mm3 iv) Total Bilirubin =\< 2.0 mg/dL v) Aspartate aminotransferase (AST) =\< 100 U/L vi) Alanine Aminotransferase (ALT) =\< 100 U/L vii) Cr =\< 1.5 mg/dL
17. Open surgery or laparoscopic surgery is planned.
18. Written informed consent is obtained.

Exclusion Criteria:

1. Synchronous or metachronous (within 5 years) malignancies except cancer with 5-year relative survival rate of 95% or more such as carcinoma in situ, intramucosal tumor, or early stage cancers.
2. Infections requiring systemic treatment.
3. Body temperature higher than 38 degrees Celsius at registration.
4. Pregnant female, female within 28 days post-parturition, or lactating mother. Men with partners planning conception in the near future.
5. Severe psychological disease.
6. Continuous systemic corticosteroid or immunosuppressant treatment.
7. Uncontrollable diabetes mellitus.
8. Uncontrollable hypertension.
9. Unstable angina pectoris, or history of myocardial infarction within 6 months.
10. Uncontrollable valvular disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy.
11. Positive serum Hepatitis B (HB)s antigen or serum Hepatitis C Virus (HCV) antibody.
12. Positive serum HIV antibody.
13. Interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT.

Primary outcomes:
measure: Locally recurrent free survival
timeFrame: 3-years after registration
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3-years after registration
measure: Recurrence free survival (RFS)
timeFrame: 3-years after registration
measure: Local relapse rate
timeFrame: 3-years after registration
measure: Distant relapse rate
timeFrame: 3-years after registration
measure: R0 resection rate
timeFrame: 1 month after surgery
measure: Response rate of preoperative chemoradiotherapy (preCRT)
timeFrame: before surgery
measure: Pathological complete response rate
timeFrame: 1 month after surgery
measure: Completeness of the protocol treatment
timeFrame: 8 months after surgery
measure: Adverse event rate
timeFrame: 3-years after surgery registration
measure: QOL
timeFrame: 3-years after registration
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Gifu
country: Japan
facility: Gifu University School of Medicine
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Asa Citizens Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hospital
city: Izumo
country: Japan
facility: Shimane University Faculty of Medicine
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kawagoe
country: Japan
facility: Saitama Medical Center, Saitama Medical University
city: Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital
city: Kurume
country: Japan
facility: Kurume University School of Medicine
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Mitaka
country: Japan
facility: Kyorin University Faculty of Medicine
city: Morioka
country: Japan
facility: Iwate Medical University
city: Nagoya
country: Japan
facility: Nagoya University Graduate School of Medicine
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine
city: Okayama
country: Japan
facility: Okayama Saiseikai General Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Sapporo
country: Japan
facility: Sapporo-Kosei General Hospital
city: Sendai
country: Japan
facility: Miyagi Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Suita
country: Japan
facility: Osaka University Graduate School of Medicine
city: Suita
country: Japan
facility: Suita Municipal Hospital
city: Takatsuki
country: Japan
facility: Osaka Medical College
city: Tokorozawa
country: Japan
facility: National Defense Medical College
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Toho University Ohashi Medical Center
city: Tokyo
country: Japan
facility: Toho University Omori Medical Center
city: Tokyo
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
city: Utsunomiya
country: Japan
facility: Tochigi Cancer Center
city: Yamagata
country: Japan
facility: Yamagata Prefectural Central Hospital
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: Yokohama
country: Japan
facility: Saiseikai Yokohama-shi Nanbu Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Yufu
country: Japan
facility: Oita University Faculty of Medicine
city: Ōgaki
country: Japan
facility: Ogaki Municipal Hospital
city: Ōta
country: Japan
facility: Gunma Prefectural Cancer Center
Study officials:
affiliation: National Cancer Center Hospital East
name: Masaaki Ito, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kadota T, Tsukada Y, Ito M, Katayama H, Mizusawa J, Nakamura N, Ito Y, Bando H, Ando M, Onaya H, Fukuda H, Kanemitsu Y. A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with preoperative chemoradiotherapy followed by surgery plus adjuvant chemotherapy for locally recurrent rectal cancer: Japan Clinical Oncology Group study JCOG1801 (RC-SURVIVE study). Jpn J Clin Oncol. 2020 Aug 4;50(8):953-957. doi: 10.1093/jjco/hyaa058.