Clinical trial NCT04801511: Preoperative IMRT With Concurrent High-dose Vitamin C and mFOLFOX6 in Locally Advanced Rectal Cancer
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal Cancer
neoadjuvant
chemoradiotherapy
Vitamin C
Lead sponsor: Zhongnan Hospital
Sponsor class: OTHER
First posted: 2021-03-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: PCR rate
timeFrame: 2 year From the first subject underwent surgery to the last subject underwent surgery.
Secondary outcomes:
measure: acute toxicity
timeFrame: 2 year
measure: Resection rate of anus preserving surgery
timeFrame: 2 year From the first subject underwent surgery to the last subject underwent surgery.
measure: 2-year survival rate
timeFrame: up to 2 years after the last subject being enrolled
measure: 2-year disease-free survival rate
timeFrame: up to 2 years after the last subject being enrolled.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Zhongnan Hopital of Wuhan University
state: Hubei
Study officials:
affiliation: Zhongnan Hospital
name: Fuxiang Zhou, M.D.
role: STUDY_CHAIR
References: