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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy of Preoperative IMRT (Intensity-modulated Radiation Therapy) With Concurrent High-dose Intravenous Vitamin C and mFOLFOX6 in Locally Advanced Rectal Cancer Patients: a Prospective Study.

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Vitamin C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years of age with a confirmed histopathologic diagnosis of adenocarcinoma of the rectum and considered suitable for curative resection. 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. 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) Laboratory examination showed that glucose-6-phosphate dehydrogenase (G6PD) was normal. The patient agreed and had signed the informed consent Exclusion Criteria: With metastatic disease. Prior radiotherapy or chemotherapy. The presence of other cancers. Clinically significant cardiac disease. Known peripheral neuropathy. With intestinal obstruction, intestinal perforation or tumor bleeding who need emergency operation. Rectal cancer with signet-ring cell carcinoma, or with Neuroendocrine tumor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Preoperative CRT: The eligible subjects will be treated with concurrent chemoradiotherapy and high-dose intravenous vitamin C. IMRT will be delivered to PTV-CTV (plan target volume-clinical target volume) with a dose of 45Gy/25f. If necessary, additional boost of 5-10Gy will be delivered to PTV-GTV (plan target volume- gross tumor volume). During the 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. Three additional cycles of chemotherapy (mFOLFOX6) will be given after radiotherapy. Radical surgery will be performed approximately 10-12 weeks after the end of radiotherapy. Whether or not to select watch and wait or sphincter preserving surgery needs to refer to the tumor location, tumor regression, surgeon's opinion and patient's will.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>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. | Drug: Vitamin C<br>* High-dose Intravenous Vitamin C will be delivered on the day of radiotherapy, in order to reduce the acute toxicity of chemoradiotherapy.<br>* Other names: ascorbic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR rate | 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. | 2 year From the first subject underwent surgery to the last subject underwent surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute toxicity | 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 | 
| Resection rate of anus preserving surgery | In patients with low rectal cancer, the percentage of subjects who underwent anus preserving surgery accounted for the total TME surgery. | 2 year From the first subject underwent surgery to the last subject underwent surgery. | 
| 2-year survival rate | 2-year survival rate of ITT (Intent to treat) population. | up to 2 years after the last subject being enrolled | 
| 2-year disease-free survival rate | 2-year disease-free survival rate of ITT population. | up to 2 years after the last subject being enrolled. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin C, Rectal Cancer, neoadjuvant, chemoradiotherapy