A Multicenter Single-arm P2 to Evaluate Safety and Efficacy of the Total Neoadjuvant Therapy for cT2 Rectal Cancer

Phase 2

Recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: Radiation; Drug: Chemotherapy; Procedure: Surgery

• Registration Number: NCT05939661
• Lead Sponsor: Osaka University

Brief Summary

A multicenter single-arm phase 2 study to evaluate safety and efficacy of the total neoadjuvant therapy of short course radiation therapy followed by neoadjuvant oxaliplatin/fluorouracil-based chemotherapy (CAPOX) for cT2 rectal cancer

Detailed Description

To evaluate the efficacy and safety of preoperative radiation therapy followed by preoperative chemotherapy and surgery for T2 advanced rectal cancer.

Study Timeline

• Study Start: 2023-05-25
• Study First Submitted: 2023-06-25
• Status Verified: 2023-07
• Study First Submitted QC: 2023-07-01
• Last Update Submitted: 2023-07-01
• Study First Posted: 2023-07-11
• Last Update Posted: 2023-07-11
• Primary Completion: 2026-03-31
• Study Completion: 2030-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• 1. The patient has been fully informed of the contents of the study and has given written consent.

  2. The patient has adenocarcinoma of the rectum confirmed by histological examination.

  3. No distant metastases are detected on imaging studies, and radical resection is clinically feasible.

  4. Age of 20 years or older on the date of consent. 5. ECOG Performance Status (PS) is 0 - 1 (PS 0 for age 71 years or older on the date of consent).

  5. Previously untreated rectal cancer with the lower margin of the tumor within 12 cm of the anal verge (AV).

  6. Patients with cT2N0M0 in the diagnosis before starting treatment (a lymph node with a short diameter of 7 mm or more is considered positive).

The conditions for lymph node metastasis shall be as follows. Contrast-enhanced CT or MRI (plain or contrast-enhanced) with a slice width of 5 mm or less.

(i) Short diameter of 10 mm or more (ii) Short diameter of 7 mm or more and one or more of the following a) to c) are met

(a) Edge irregularity (b) Low signal area with internal heterogeneity on MRI (c) Circular (long/short diameter ratio < 1.5) If contrast-enhanced CT is not possible due to contrast medium allergy, renal dysfunction, or bronchial asthma, simple CT is acceptable.

8. The following criteria for major organ function within 14 days prior to registration are met.

If more than one test result exists within this period, the most recent one should be used. No blood transfusions or hematopoietic factor products should be administered within 14 days prior to the test date.

1. Neutrophil count: greater than or equal to 1,500/mm3
2. Platelet count: >= 10.0 x 104 /mm3
3. Hemoglobin concentration: >=9.0 g/dL
4. Total bilirubin: 1.5 times or less than the upper limit of the institutional standard
5. AST, ALT, ALP: 2.5 times or less than the upper limit of the institutional standard
6. Serum creatinine: 1.5 times or less than the upper limit of the institutional standard or creatinine clearance: 45 mL/min or more

Exclusion Criteria

• 1. underwent treatment by any of the following within a certain period of time prior to initiation of protocol therapy

  2. extensive surgery (excluding CV port placement) within 4 weeks

  3. Any anticancer therapy within 4 weeks

  4. Radiation within 4 weeks 2. concomitant or pre-existing severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.) 3. patients who have had a colonic stent implanted 4. patients with serious comorbidities (heart failure, renal failure, liver failure, bleeding peptic ulcer, intestinal paralysis, bowel obstruction, poorly controlled diabetes, etc.) 5. patients with active multiple overlapping cancers (synchronous multiple overlapping cancers or iatrogenic multiple overlapping cancers with a disease-free period of 5 years or less). However, carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma that is considered curable by local treatment is not considered active multiple overlapping carcinoma.

     6. pregnant or lactating women, positive pregnancy test or unwillingness to use contraception 7. HBs antigen positive or HCV antibody positive. 8. has known human immunodeficiency virus (HIV) infection. 9. otherwise judged by the principal investigator or subinvestigator to be unsuitable for this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
TNT	Radiation	Neoadjuvant radiation therapy : 5Gyx5 Neoadjuvant chemo therapy : CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Operation: Total methorectum excision wiht radical lymph node dissection
TNT	Chemotherapy	Neoadjuvant radiation therapy : 5Gyx5 Neoadjuvant chemo therapy : CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Operation: Total methorectum excision wiht radical lymph node dissection
TNT	Surgery	Neoadjuvant radiation therapy : 5Gyx5 Neoadjuvant chemo therapy : CAPOX (Oxaliplatin 130mg/m2, Capecitabine2000mg/m2/day, d1-14, 3week)x6cycles Operation: Total methorectum excision wiht radical lymph node dissection

Primary Outcome Measures

Name	Time	Method
Pathological complete response (pCR)	through study completion, an average of 6 months	pCR is evaluated by using the grading scale according to the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma

Trial Locations

Locations (2)

Osaka General Medical Center; 🇯🇵 Osaka, Japan

Osaka University Hospital; 🇯🇵 Osaka, Japan