Preoperative IMRT With Concurrent High-dose Vitamin C and mFOLFOX6 in Locally Advanced Rectal Cancer

Phase 2

Recruiting

• Conditions: Rectal Cancer
• Interventions: Drug: Vitamin C

• Registration Number: NCT04801511
• Lead Sponsor: Zhou Fuxiang

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of preoperative chemoradiotherapy (IMRT) with concurrent high-dose intravenous vitamin C and mFOLFOX6 in locally advanced rectal cancer patients.

Detailed Description

Sixty patients with locally advanced rectal cancer (cT3-4N0M0, cT1-4N1-2M0, ≤12cm from anus) will be enrolled and receive preoperative IMRT concurrent with high-dose intravenous vitamin C and 2-3 cycles of mFOLFOX6 chemotherapy, and then after 4 weeks rest, they will continue to complete 3 cycles of preoperative chemotherapy (mFOLFOX6). Radical surgery will be performed at 10-12 weeks after IMRT.

In this study, we will evaluate the safety and effectiveness of the treatment method through the acute toxicity \[during CRT (concurrent chemoradiotherapy )\], PCR (pathologic complete response) rate, sphincter preserving surgery rate, 2-year survival rate and 2-year disease-free survival rate.

Study Timeline

• Status Verified: 2021-03
• Study Start: 2021-03-08
• Study First Submitted: 2021-03-11
• Study First Submitted QC: 2021-03-15
• Last Update Submitted: 2021-03-15
• Study First Posted: 2021-03-17
• Last Update Posted: 2021-03-17
• Primary Completion: 2023-06-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. 18 to 75 years of age with a confirmed histopathologic diagnosis of adenocarcinoma of the rectum and considered suitable for curative resection.
2. Tumors were clinically confirmed (by MRI or CT plus endorectal ultrasound) as stage II (cT3-4N0) or stage III (cT1-4N1-2), with a positive node defined as ≥1.0 cm in diameter on imaging) and a distal border located , 12 cm from the anal verge.
3. Patients were required to have an Eastern Cooperative Oncology Group performance status ≤ 1 and adequate hematologic, liver, and renal function. (HGB≥90g/L, WBC≥3.5×10^9/L, PLT≥90×10^9/L；ALT / AST≤2.5× ULN；T BILL≤1.5×ULN，Cr ≤1.5×ULN)
4. Laboratory examination showed that glucose-6-phosphate dehydrogenase (G6PD) was normal.
5. The patient agreed and had signed the informed consent

Exclusion Criteria

1. With metastatic disease.
2. Prior radiotherapy or chemotherapy.
3. The presence of other cancers.
4. Clinically significant cardiac disease.
5. Known peripheral neuropathy.
6. With intestinal obstruction, intestinal perforation or tumor bleeding who need emergency operation.
7. Rectal cancer with signet-ring cell carcinoma, or with Neuroendocrine tumor.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Vitamin C	Preoperative concurrent chemoradiotherapy and high-dose intravenous vitamin C : The eligible subjects will be treated with concurrent chemoradiotherapy and high-dose intravenous vitamin C preoperatively. IMRT will be delivered to PTV-CTV (plan target volume-clinical target volume) with a dose of 45Gy/25fraction/5weeks. If necessary. During IMRT, 2-3 cycles of concurrent chemotherapy (mFOLFOX6) will be delivered. High-dose intravenous vitamin C ( 24g/d，QD ) will be delivered on the day of radiotherapy from the beginning to the end of IMRT. preoperative consolidation chemotherapy: Three additional cycles of neoadjuvant chemotherapy (mFOLFOX6) will be given after the end of IMRT. TME （total mesorectal excision）or sphincter preserving surgery will be performed approximately the 10th-12th weeks after the end of IMRT. Whether or not to select "watch and wait" needs to refer to the tumor location, tumor regression, surgeon's opinion and patient's will.

Primary Outcome Measures

Name	Time	Method
PCR rate	2 year From the first subject underwent surgery to the last subject underwent surgery.	The PCR rate is defined as the percentage of subjects who achieved Pathological complete remission（PCR） in the total number of the subjects who underwent surgery in the ITT population.

Secondary Outcome Measures

Name	Time	Method
2-year survival rate	up to 2 years after the last subject being enrolled	2-year survival rate of ITT (Intent to treat) population.
Resection rate of anus preserving surgery	2 year From the first subject underwent surgery to the last subject underwent surgery.	In patients with low rectal cancer, the percentage of subjects who underwent anus preserving surgery accounted for the total TME surgery.
acute toxicity	2 year	acute toxicity including diarrhea， vomiting leukopenia, er al, during the preoperative CRT and high-dose intravenous vitamin C and 30 after the radiotherapy.
2-year disease-free survival rate	up to 2 years after the last subject being enrolled.	2-year disease-free survival rate of ITT population.

Trial Locations

Locations (1)

Zhongnan Hopital of Wuhan University; 🇨🇳 Wuhan, Hubei, China