A Randomized, Phase III Controlled Study to Compare CAPOX Therapy as Post-operative Adjuvant Chemotherapy with Surgery Alone in Patients with Completely Resected Circulating Tumor DNA-negative High-risk Stage II and Low-risk Stage III Colon Cancer

JRCT ID: jRCT1031200006

Registered date:08/04/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Colon Cancer
• Date of first enrollment: 01/04/2020
• Target sample size: 1000
• Study type: Interventional

Intervention(s)

At enrollment, protocol treatment will be assigned to each subject. If the patient has been assigned to the control group (Group S), CAPOX therapy should be initiated within 2 weeks after the enrollment (the same day of the week as the date of enrollment is acceptable).
[Control group: Group S (3-month CAPOX therapy group)]
CAPOX therapy consists of 3 weeks per a cycle, which will be repeated for 4 cycles (12 weeks). After completing the protocol treatment, follow-up will be performed without treatment until relapse. However, if ctDNA becomes positive, participating in the ALTAIR study for treatment is acceptable. The use of generic drugs in both oxaliplatin and capecitabine is acceptable.
[Group T: Surgery alone]
After enrollment, follow-up will be performed without treatment until relapse. However, if ctDNA becomes positive, participating in the ALTAIR study for treatment is acceptable.

Outcome(s)

Primary Outcome

(1)Disease-free survival* (DFS*)
*In the CIRCULATE-IDEA study, a DFS event will be defined as, following the definition in the IDEA study, a relapse, an occurrence of second-onset colorectal cancer lesion (except for intramucosal cancer lesions) other than the relapse which is confirmed at the first time since the date of enrollment, or a death due to any cause.

Secondary Outcome

(1)Disease-free survival 2* (DFS2*)
*An event is defined as a relapse, an occurrence of cancer lesions other than relapse (secondary cancer), and a death.
(2)Time to Treatment Failure (TTF)
(3)Overall Survival (OS)
(4)Adverse Events (AE)
(5)Treatment completion rate
(6)Relative Dose Intensity (RDI)
(7)Investigation of clinicopathological molecular biological background and prognosis
(8)Peripheral sensory/motor neuropathy
(9)ctDNA negative rate at each timepoint
(10)Proportion of treatment-related amenorrhea in women of reproductive age

Key inclusion & exclusion criteria

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

Include criteria

(1)Histopathological diagnosis has been made as primary colonic adenocarcinoma.
(2)Based on the operative findings and resected specimen findings, the primary location of the tumor is the colon*. *Includes the rectosigmoid part defined in the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, Ninth Edition.
(3)A colectomy including systematic lymph node dissection of D2 or D3 has been performed.
(4)At the time of completion of surgery, residual cancer is considered to be R0.
(5)The disease stage based on overall findings is high-risk Stage II (having at least one of the following risk factors (a) to (f) for relapse), or low-risk Stage III (T1-3N1M0) (UICC TNM Classification, 8th Edition).*
*N1c (UICC TNM Classification, 8th Edition) is also considered to be eligible (tumor deposits, or satellite nodules, are seen in the adjacent soft tissues of the colon or rectum without subserosal layer or peritoneal coat, but no regional lymph node metastasis)
(a)T4 (SE/SI/AI)
(b)Intestinal tract obstruction (clinical)
(c)Intestinal tract perforation/penetration (clinical)
(d)Less than 12 dissected lymph nodes
(e)Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma
(f)Positive for lymphatic invasion, venous invasion, or neuroinvasion
(6)Negative ctDNA at 28 days+-7 days* post-operatively (the same day of the week as the surgery day is accepted).**
*Delays within one week are allowed on public holidays, year-end and New Year holidays, and due to patient visits.
**The results of ctDNA testing are based on the test results in the Registry Research in Potentially Surgically Curative Colorectal Cancer.
(7)Enrollment can be performed within 8 weeks* after the curative resection and treatment can be started within 2 weeks after the enrollment.
*Delays less than three weeks are allowed due to public holidays, year-end and New Year holidays, patient visits, delays in returning ctDNA results, etc.
(8)The age at the time of acquisition of informed consent is 20 years or older.
(9)Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
(10)No history of chemotherapy, immunotherapy, or radiotherapy within 6 months prior to enrollment, including treatment for other types of cancer.
(11)The organ function is met according to the following laboratory values measured within 14 days prior to enrollment (tests performed on the same day of the week 14 days prior to enrollment are acceptable).
Neutrophil count:>=1,500 /mm3 (exclude measurement values within 14 days after administration of granulocyte colony-stimulating factor [G-CSF])
Platelet count:>=100,000 /mm3
Creatinine clearance:>=30 mL/min
Total bilirubin:<=2.0 mg/dL
AST and ALT:<=100 IU/L
CEA:<=10ng/mL
(12)Voluntary consent to participation in the study has been obtained.

Exclude criteria

(1)There are 2 or more infiltrating cancers of the large intestine origin at the same time. An infiltrating cancer is defined as cancer infiltrating to the submucosa or deeper, and does not include intramucosal cancer.
(2)History of a malignant tumor.*
*Patients with a relapse-free survival period of 5 years or longer, or patients with basal cell or squamous cell carcinoma of that skin that is considered cured by local treatment, superficial bladder cancer, cervical cancer, carcinoma in situ (intraepithelial cancer) or lesions equivalent to intramucosal cancer, or non-metastatic prostate cancer not requiring systemic treatment may be enrolled.
(3)Test using tumor samples shows BRAF V600E mutant type.*( If analysis is not possible, can register)
*The results of BRAF testing are based on the test results in the Registry Research in Potentially Surgically Curative Colorectal Cancer.
(4)Test using tumor samples shows MSI-H.* (If analysis is not possible, can register)
*The results of MSI testing are based on the test results in the Registry Research in Potentially Surgically Curative Colorectal Cancer.
(5)Pregnant or breastfeeding women.
(6)Patients who do not agree to contraception during treatment and up to 30 days after treatment
(7)Patients with complications of uncontrolled infections.
(8)Patients with peripheral sensory/motor neuropathy.
(9)Patients with complications of uncontrolled diabetes.
(10)Patients with complications of uncontrolled congestive heart failure, angina, hypertension, or arrhythmia.
(11)Continuous systemic administration of steroids (>= 10 mg/day of prednisolone equivalent) (either oral or IV administration).
(12)History or complication of neurologically or mentally significant illness.
(13)Positive HBs antigen or positive HCV antibody.
(14)Positive HIV antibody (a patient may enroll even if HIV antibody has not been tested).
(15)Known deficiency of dihydoropyrimidine dehydrogenase (DPD).
(16)History of allergy to oxaliplatin and/or capecitabine.
(17) There is an active new corona infection (COVID-19)*.
* Known SARS-CoV-2 PCR positive patients or patients with suspected COVID-19 due to clinical symptoms. Patients with negative SARS-CoV-2 PCR and no COVID-19 symptoms can be enrolled, but excluded if the attending physician determines that it will affect the evaluation of this study (COVID -19 inspection is not mandatory).
(18)Any other cases which are judged to be inappropriate for participation in this clinical study by a physician.

Related Information

• Primary Sponsor: Takemasa Ichiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED),Alpha-A, Inc.,National Cancer Center Japan
• Secondary ID(s): -