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

Sponsor

Zhou Fuxiang (Other)

Overall Status

Recruiting

CT.gov ID

NCT04801511

Collaborator

(none)

Enrollment

Location

Arm

45.8

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Vitamin C	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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.

Anticipated Study Start Date :

Mar 8, 2021

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental 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 High-dose Intravenous Vitamin C will be delivered on the day of radiotherapy, in order to reduce the acute toxicity of chemoradiotherapy. Other Names: ascorbic acid

Arm

Intervention/Treatment

Experimental: Experimental

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

High-dose Intravenous Vitamin C will be delivered on the day of radiotherapy, in order to reduce the acute toxicity of chemoradiotherapy.

Other Names:

ascorbic acid

Outcome Measures

Primary Outcome Measures

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

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.
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.
2-year survival rate [up to 2 years after the last subject being enrolled]
2-year survival rate of ITT (Intent to treat) population.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.