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

• ClinicalTrials.gov Identifier: NCT04801511
• Recruitment Status: Recruiting
• First Posted: March 17, 2021
• Last Update Posted: March 17, 2021
• Sponsor: Zhou Fuxiang
• Information provided by (Responsible Party): Zhou Fuxiang, Zhongnan Hospital

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 (Clinical Trial)
• Estimated 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.
• 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.
• Estimated Study Start Date: March 8, 2021
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: December 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 Name: ascorbic acid

Outcome Measures

Primary Outcome Measures :

1. PCR rate [ Time Frame: 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 :

1. acute toxicity [ Time Frame: 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. Resection rate of anus preserving surgery [ Time Frame: 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.
3. 2-year survival rate [ Time Frame: up to 2 years after the last subject being enrolled ]
   2-year survival rate of ITT (Intent to treat) population.
4. 2-year disease-free survival rate [ Time Frame: up to 2 years after the last subject being enrolled. ]
   2-year disease-free survival rate of ITT population.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Fuxiang Zhou, M.D.; 08602767813155; fuxiang.zhou@whu.edu.cn

Locations

China, Hubei

Zhongnan Hopital of Wuhan University; Recruiting

Wuhan, Hubei, China, 430071

Contact: Fuxiang Zhou, M.D +86-027-67813155 happyzhoufx@sina.com

Sponsors and Collaborators

Zhou Fuxiang

Investigators

• Study Chair: Fuxiang Zhou, M.D.; Zhongnan Hospital

More Information

• Responsible Party: Zhou Fuxiang, professor, Zhongnan Hospital
• ClinicalTrials.gov Identifier: NCT04801511
• Other Study ID Numbers: HCCSC R02
• First Posted: March 17, 2021
• Last Update Posted: March 17, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zhou Fuxiang, Zhongnan Hospital:

Rectal Cancer; neoadjuvant; chemoradiotherapy; Vitamin C

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Ascorbic Acid; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents