Clinical trial NCT02280070: RP II Study of SOX vs mFOLFOX6 in Patients With Resectable Rectal Cancer (KSCC1301).
Official title: Randomized Phase II Study of SOX vs mFOLFOX6 as Neoadjuvant Chemotherapy in Patients With Resectable Rectal Cancer (KSCC1301).
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: resectable rectal cancer
SOX
mFOLFOX6
neoadjuvant
Lead sponsor: Clinical Research Support Center Kyush
Sponsor class: OTHER
First posted: 2014-10-31
Enrollment: 110
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of SOX or mFOLFOX6 as neoadjuvant chemotherapy in patients with resectable rectal cancer, and to identify the more promising regimen.

Detailed description: 1. Patient registration procedure

If it is confirmed that the subject meets the inclusion criteria and correspondent none of the exclusion criteria, the subject is registered by using CReS Kyushu registration/allocation system (CK-RAS). The registration with CK-RAS is available for 24hr (URL: https://reg.cres-kyushu.or.jp/qmin/login/) and needs for individual ID and password.

2. Quality management

1. Monitoring

   A central monitoring or in-site monitoring are carried out based on the data from case report form (CRF) collecting at data coordinating center. In principle, an on-site monitoring is not carried out, but it may be carried out when the on-site monitoring is determined to need by Kyushu Study group of Clinical Cancer (KSCC) steering committee from the results of the central monitoring so on.
2. Data Monitoring Committee

   A Data Monitoring Committee (DMC) has been established.
3. Data entry

   All data will be entered by the double entry method. Referential data rules, valid values, range checks, and consistency checks against data already stored in the database will be supported. Checks will be applied at the time of data entry into a specific field. Additional errors will be detected by programs designed to detect missing data or specific errors in the data. The investigator who receives the inquiry will respond by checking the original forms for inconsistency, checking other sources to determine the correction, modifying the original paper form entering a response to the query.
4. Regular monitoring report

   A regular monitoring report generated by data coordinating center is submitted to KSCC Steering Committee, principal investigator, the DMC etc and it is reviewed according to "KSCC regulation on the monitoring". The information on the status of site EC approval and the achievement of enrollment: number of enrollment- total/per periodical, total/per site, is reported monthly using e-mail.
   * Contents of monitoring report

     1. Study abstract: schema/purpose/subject/endpoint/definition of treatment/anticipated enrollment number/progress of the study
     2. Enrollment status: per participating site/total
     3. Monitoring activity: contents of activity/CRF collection per site/uncollected CRF, inquiry
     4. Review of the eligible treatment case：the case of ineligible possibility/the case determined as ineligible/number of eligible case/the case determined as non-treatment/total number of treatment case
     5. Review of a target population for analysis: the number of cases targeted for efficacy analysis/safety analysis
     6. Patient background
     7. Treatment time-course: summary of on-treatment and discontinuation/summary of reason for discontinuation/list of reason for discontinuation
     8. Protocol violation/deviation
     9. Safety evaluation: serious adverse reaction, event/the case which was notified to the study group among the adverse reactions, events with an ordinary report/general adverse events
     10. Others
5. Audit

A site audit is carried out by the audit members of KSCC Coordinating Center, data coordinating center, medical staff of other site under the approval of the site director according to "KSCC regulation for site audit". The results of the audit are reported to the site director, KSCC Steering Committee, principal investigator etc. (if required, to DMC).

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Patients who are judged to be suitable for receiving this protocol therapy by physician
* Distal border of tumor is located under the peritoneal reflection
* Histologically confirmed rectal adenocarcinoma
* Previously untreated rectal cancer
* Within 28 days before registration, the tumor is considered by the surgeon to be amenable to curative resection \[T category: cSS and cSE, cSI, cA, cAI. N category: cN0-2 and cN3(#253 lymph node)\]
* Within 28 days before registration, there is no evidence of distant metastasis by contrast-enhanced CT
* \>= 20 years old
* PS (ECOG) 0-1
* Be able to take oral drugs
* Required baseline laboratory parameters (within 14 days before registration): WBC \>= 3000 ,\<12000/mm3, Neu \>= 1,500/ mm3, Hb \>= 9.0g/dl, Plt \>= 100,000/ mm3, T-Bil \<= 2.0mg/dl, AST,ALT \<= 100U/L, Cre \<1.5mg/dl, Ccr \>= 60mL/min
* Considered to survive for more than 3 months

Exclusion Criteria:

* History of serious drug hypersensitivity or a history of drug allergy
* Pregnant or lactating woman and man who hope for Partner's pregnant
* Active infection(over 38 degree)
* Serious complication ( ex. interstitial pneumonitis, pulmonary fibrosis, renal failure, liver failure, serious diabetes, serious hypertension)
* Clinically significant abnormal electrocardiogram or heart disease
* Serious diarrhea
* Pleural effusion, peritoneal fluid that needs treatment
* Previous history of serious lung disorder ( ex. interstitial lung disease or fibrosis, serious emphysema )
* Hemorrhagic diathesis, coagulation disorder
* Active double cancer (synchronous double cancer or asynchronous double cancer with disease-free duration of 5 years or less)
* Patients who need flucytosine, phenytoin or warfarin potassium
* Requiring steroid drug
* Patients with contraindication to therapy
* History of allergy to contrast material
* Serious stricture (exclude the patients who are put in stoma)
* Positive for HBs antigen and HCV antibody
* Not appropriate for the study at the physician's assessment

Primary outcomes:
measure: 3-years Disease Free Survival rate
timeFrame: 3 years from the enrollment
Secondary outcomes:
measure: Pathological Effect
timeFrame: After operation, up to 5 years after the last subject enrollment.
measure: R0 resection rate
timeFrame: At operation, up to 5 years after the last subject enrollment.
measure: Completion rate of each modality (neoadjuvant chemotherapy, operation and adjuvant chemotherapy)
timeFrame: After completion of protocol treatment, up to 5 years after the last subject enrollment.
measure: Overall survival (OS)
timeFrame: Up to 5 years after the last subject enrollment.
measure: Disease Free survival (DFS)
timeFrame: The date of recurrence, occurrence of secondary cancer and death, up to 5 years after the last subject enrollment.
measure: OS in patients with R0 resection
timeFrame: At the date of death, up to 5 years after the last subject enrollment.
measure: DFS in patients with R0 resection
timeFrame: The date of recurrence, occurrence of secondary cancer and death, up to 5 years after the last subject enrollment.
measure: Transition rate to Operation
timeFrame: At the operation, up to 5 years after the last subject enrollment.
measure: local recurrence rate (per operated population)
timeFrame: After the operation, up to 5 years after the last subject enrollment.
measure: Safety
timeFrame: Within protocol treatment, up to 5 years after the last subject enrollment.
measure: Pattern of first recurrence
timeFrame: At the study completion, up to 5 years after the last subject enrollment.
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kurume
country: Japan
facility: Kurume University Hospital
Study officials:
affiliation: Saiseikai Fukuoka General Hospital
name: Yasunori Emi, MD, PhD
role: STUDY_DIRECTOR
References: