Surgery Plus Chemo Versus Chemoradiotherapy Followed by Surgery Plus Chemo for Locally Recurrent Rectal Cancer

Rectal Cancer Recurrent Clinical Trial

— JCOG1801  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04288999
• Other study ID #: JCOG1801
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2019
• Est. completion date: October 2028

Study information

• Verified date: June 2020
• Source: National Cancer Center Hospital East
• Contact: Yuichiro Tsukada, MD,PhD
• Phone: +80-4-7133-1111
• Email: yutsukad[@]east.ncc.go.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: October 2028
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer Recurrent
• Rectal Neoplasms

Intervention

Drug:
• Chemotherapy
Adjuvant chemotherapy: CAPOX or mFOLFOX6 or capecitabine or 5-FU+l-LV CAPOX: oxaliplatin (130 mg/m2/day, day 1) and oral capecitabine (2000 mg/m2/day, twice daily, days 1-14) mFOLOX6: oxaliplatin 85 mg/m2 with l-LV 200 mg/m2 for over 2 hours followed by a fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion over 46 hours. Capecitabine: 2000 mg/m2/day, twice daily, days 1-14 5-FU+l-LV: leucovorin 200 mg/m2 for over 2 hours followed by a fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion for over 46 hours

Radiation:
• Preoperative radiotherapy
Preoperative chemoradiotherapy (CRT) followed by Surgery plus Adjuvant chemotherapy Preoperative CRT: capecitabine (1650 mg/m2/day) and radiotherapy (50.4 Gy/28 Fr)

Other:
• Procedure
Surgery for Locally Recurrent Rectal Cancer (LRRC) will be performed within 42 days from registration for the patients in arm A, and between days 56 and 98 from the completion of the preCRT for the patients in arm B. Appropriate surgical procedure will be performed to achieve R0 resection, such as low anterior resection, super low anterior resection, intersphincteric resection, Hartmann procedure, rectal amputation, pelvic exenteration, tumor resection, or lateral lymph node dissection

Locations

Country	Name	City	State
Japan	Chiba Cancer Center	Chiba
Japan	Gifu University School of Medicine	Gifu
Japan	Saitama Medical University International Medical Center	Hidaka
Japan	Kansai Medical University Hospital	Hirakata
Japan	Hiroshima City Asa Citizens Hospital	Hiroshima
Japan	Hiroshima City Hospital	Hiroshima
Japan	Shimane University Faculty of Medicine	Izumo
Japan	Ishikawa Prefectural Central Hospital	Kanazawa
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Saitama Medical Center, Saitama Medical University	Kawagoe
Japan	Kochi Health Sciences Center	Kochi
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kurashiki Central Hospital	Kurashiki
Japan	Kurume University School of Medicine	Kurume
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama
Japan	Kyorin University Faculty of Medicine	Mitaka
Japan	Iwate Medical University	Morioka
Japan	Nagoya University Graduate School of Medicine	Nagoya
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Hyogo College of Medicine	Nishinomiya
Japan	Ogaki Municipal Hospital	Ogaki
Japan	Okayama Saiseikai General Hospital	Okayama
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Osaka City General Hospital	Osaka
Japan	Gunma Prefectural Cancer Center	Ota
Japan	Saitama Cancer Center	Saitama
Japan	Sapporo-Kosei General Hospital	Sapporo
Japan	Miyagi Cancer Center	Sendai
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Osaka University Graduate School of Medicine	Suita
Japan	Suita Municipal Hospital	Suita
Japan	Osaka Medical College	Takatsuki
Japan	National Defense Medical College	Tokorozawa
Japan	National Cancer Center Hospital	Tokyo
Japan	Toho University Ohashi Medical Center	Tokyo
Japan	Toho University Omori Medical Center	Tokyo
Japan	Tokyo Medical and Dental University Hospital	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Tokyo
Japan	Tochigi Cancer Center	Utsunomiya
Japan	Yamagata Prefectural Central Hospital	Yamagata
Japan	Kanagawa Cancer Center	Yokohama
Japan	Saiseikai Yokohama-shi Nanbu Hospital	Yokohama
Japan	Yokohama City University Medical Center	Yokohama
Japan	Oita University Faculty of Medicine	Yufu

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Center Hospital East	Japan Agency for Medical Research and Development, Japan Clinical Oncology Group

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Locally recurrent free survival	the period from registration in the trial to either the first event of local relapse or death from any cause and censored at the last date of contact for a living patient	3-years after registration
Secondary	Overall survival (OS)	s the time from registration to death from any cause and censored at the last date of contact for a living patient	3-years after registration
Secondary	Recurrence free survival (RFS)	the time from registration to either the first incidence of relapse or death from any cause and censored at the last date of contact for a living patient	3-years after registration
Secondary	Local relapse rate	Proportion of local relapse	3-years after registration
Secondary	Distant relapse rate	Proportion of distant relapse	3-years after registration
Secondary	R0 resection rate	Proportion of patients with pathological R0 resection	1 month after surgery
Secondary	Response rate of preoperative chemoradiotherapy (preCRT)	Response rate of preCRT (arm B)	before surgery
Secondary	Pathological complete response rate	Pathological complete response rate (arm B)	1 month after surgery
Secondary	Completeness of the protocol treatment	Proportion of patients who completed the protocol treatment	8 months after surgery
Secondary	Adverse event rate	Incidence of adverse events (adverse reactions)	3-years after surgery registration
Secondary	QOL	QOL after surgery based on the Trial Outcome Index-Physical/Functional/Colorectal (TOI-PFC) [0(better)-84(worse)]	3-years after registration

External Links

•   Japan Registry of Clinical Trials