Total Neoadjuvant Therapy in Rectal Cancer

A Phase II Study of Total Neoadjuvant Therapy in Rectal Cancer

In this phase 2 study, the efficacy of total neoadjuvant therapy in Taiwanese patients with rectal cancer will be investigated. Patients with stage II or III middle/low rectal cancer will be prospective enrolled. The total neoadjuvant therapy with the short-course radiotherapy (5×5 Gy over a maximum of 8 days) followed by chemotherapy with mFOLFOX6 for 9 cycles will be administered. The primary endpoint is the complete response (CR) rate which will take into account the patients with clinical and pathological complete response.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Short-course radiotherapy; Drug: mFOLFOX6

Detailed Description

This is a single center, single-arm, open-label, phase II study to investigate the efficacy and toxicities of total neoadjuvant therapy in patients with middle or lower rectal cancer. This study is planned to start after the approval by IRB, enroll patients for 2 years, and follow the clinical outcome for another 5 years. It will be conducted at National Cheng Kung University Hospital. Forty-two subjects will be enrolled. Patients who have newly diagnosed stage II or III, middle or low rectal adenocarcinoma will be recruited to receive the TNT treatment. The TNT includes the short-course radiotherapy (5×5 Gy over a maximum of 8 days)) followed by chemotherapy with the regimen of mFOLFOX6 for total 9 cycles

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu-Min Yeh, MD; Phone Number: 6550 +886 353535; Email: i5485111@gmail.com

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital
    • Principal Investigator: Yu-Min Yeh, MD
    • Contact: Yu-Min Yeh, MD; Phone Number: 4289 886-6-2353535; Email: i5485111@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum;
• Tumors located at mid or low rectum (distal extension less than 10 cm from the anal verge);
• Clinical stage II or III (T3/4 and/or N+; no distant metastasis);
• No prior chemotherapy, radiotherapy or surgery for rectal cancer;
• Age ≥20;
• ECOG 0-1;
• Adequate organ function, including followings:

ANC ≥1,500/μL; Hb ≥8.0 gm/dL; Platelet 100,000/mm3; Total bilirubin ≤1.5x upper normal limit; AST ≤3x upper normal limit; ALT ≤3x upper normal limit; Creatinine ≤1.5x upper normal limit;

• Ability to understand and the willingness to sing a written informed consent.

Exclusion criteria

• Recurrent rectal cancer;
• Patients who have concomitant malignancies, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix. Subjects who have prior malignancies and have been disease-free for more than 5 years can be enrolled;
• Patients who have received prior pelvic radiotherapy;
• Patients with active infection requiring intravenous antibiotic treatment;
• Patients with a history of any arterial thrombotic event within the past 6 months, including unstable angina, myocardial infarction (MI) or cerebrovascular accident (CVA), New York Hear Association (NYHA) grade II or greater congestive heart failure, or uncontrolled cardiac arrhythmia;
• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgement, would make them inappropriate candidates for entry into this study;
• Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period;
• Patients receiving other anticancer or experimental therapy;
• Known DPD deficiency or hypersensitivity to oxaliplatin;
• Any contraindications to MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; The total neoadjuvant therapy with the short-course radiotherapy (5×5 Gy over a maximum of 8 days) followed by chemotherapy with mFOLFOX6 for 9 cycles will be administered.	Radiation: Short-course radiotherapy; Short-course radiotherapy, 5×5 Gy.; Other Names: RT; Drug: mFOLFOX6; Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, infusinal 5-fluorouracil 2400 mg/m2 every 2 weeks, for 9 cycles; Other Names: Consolidation chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR) rate	The percentage of patients who achieve a complete response	The response will be assessed at the period of 2 to 4 weeks after the completion of total neoadjuvant chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	The percentage of patients who receive the surgery of total neoadjuvant therapy and achieve R0 resection	The R0 resection rate will be assessed at the period of 2 to 4 weeks after completion of the total neoadjuvant chemotherapy
Response rate	The percentage of patients who achieve a complete response or partial response	The response will be assessed at the period of 2 to 4 weeks after the completion of total neoadjuvant chemotherapy
Loco-regional failure rate	The percentage of patients who develop local recurrence after surgery	The loco-regional failure will be assessed from the date of surgical resection until the first documented local recurrence, up to 84 months
Rate of distant metastasis	The percentage of patients who develop distant metastasis	The distant metastasis will be assessed from the date of beginning short-course RT until the first documented distant metastasis, up to 84 months
Safety profiles	The occurrence and severity of adverse events which develop during the treatment of total neoadjuvant therapy	The safety profile will be assessed from the beginning of the short-course RT to the end of last cycle of FOLFOX chemotherapy, up to 24 weeks

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Investigators: Principal Investigator: Yu-Min Yeh, MD, National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): November 16, 2026
• Study Completion (Estimated): November 16, 2030

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Estimated): December 8, 2023

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: B-BR-112-042

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No