Trial Title:
Short-course Radiotherapy or Long-course Chemoradiation Followed by mFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal Cancer
NCT ID:
NCT06417476
Condition:
Rectal Neoplasms
Conditions: Official terms:
Rectal Neoplasms
Capecitabine
Fluorouracil
Oxaliplatin
Irinotecan
Calcium
Conditions: Keywords:
Neoadjuvant chemotherapy
Preoperative radiotherapy
Chemoradiotherapy
Consolidation chemotherapy
mFOLFOXIRI
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Short-course radiotherapy
Description:
The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume
without a boost dose
Arm group label:
Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
150 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Arm group label:
Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
85 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Arm group label:
Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Drug
Intervention name:
Calcium Formate
Description:
400 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Arm group label:
Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
2400 mg/m² iv drip over 48 hours on day 1-2, repeated every 14 days.
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Arm group label:
Short-course radiotherapy followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Radiation
Intervention name:
Long-course chemoradiation
Description:
The total dosage was 50Gy consisted of 25 fractions of 2 Gy to clinical target volume
without a boost dose
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
825 mg/m² twice daily administered orally and concurrently with radiation therapy for 5
days per week.
Arm group label:
Long-course chemoradiation followed by consolidation chemotherapy with mFOLFOXIRI
Summary:
Given the growing focus on preserving organ function and the utilization of neoadjuvant
therapy, it is important to investigate and enhance the application of comprehensive
neoadjuvant therapy in low rectal cancer. This approach aims to improve disease-free
survival (DFS), while minimizing or circumventing the organ dysfunction and subsequent
decline in quality of life associated with radical surgery. Consequently, we propose to
initiate a multicenter clinical trial to examine the medium- and long-term effectiveness
of complete neoadjuvant therapy (comprising either short-course radiotherapy or
long-course chemoradiation, followed by consolidation chemotherapy with mFOLFOXIRI) in
increasing organ preservation rates in patients with low rectal cancer.
Detailed description:
This randomised, open-label, multicentre,phase II trial began in December, 2022, as a
neoadjuvant trial about short-course radiotherapy or long-course chemoradiation followed
by mFOLFOXIRI consolidation chemotherapy,in patients aged 18 years to 70 with clinical
stage II-III locally advanced low rectal cancer from six Chinese institutions.
Patients with local advanced rectal cancer (cT2-4aN0-2,M0, 8cm from the anus verge) were
recruited. Patients receive short-course radiotherapy (25Gy/5 times) followed by
consolidation chemotherapy lor ong-course chemoradiation (50Gy/25 times;capecitabine 825
mg/m² twice daily) with mFOLFOXIRI (Irinotecan 150 mg/m2 iv gtt (2h) d1, Oxaliplatin 85
mg/m2 iv gtt (2h) d1, Calcium folinate 400 mg/m2 iv gtt (2h) d1, Total amount of
fluorouracil 2400 mg/m2 iv gtt (48h)), treatment repeats every 14 days for 4 courses in
the absence of disease progression or unacceptable toxicity. The first efficacy
evaluation occurs after the fourth chemotherapy cycle. Patients showing a complete
response (CR), partial response (PR), or stable disease (SD) with reduction or stability
in tumor size are advised to continue and complete all planned consolidation
chemotherapy. However, if the evaluation indicates stable disease with an increase (SD
increased) or progressive disease (PD), and if an R0 resection (complete removal of the
tumor with no cancer cells at the margins) is feasible, radical total mesorectal excision
(TME) should be pursued. In cases where R0 resection is not achievable, the treatment
should align with the guidelines for managing unresectable rectal cancer. Upon the final
efficacy assessment after the eighth chemotherapy cycle, several pathways are considered
based on the outcomes: patients achieving a clinical complete response (cCR) may proceed
to a Watch & Wait approach. Those with a near clinical complete response (near cCR)
undergo local transanal resection. If the patient's condition is evaluated as PR/SD with
a reduction but does not qualify as near cCR, radical TME is recommended. For patients
showing SD with an increase or PD, yet with a potential for R0 resection, radical TME is
again the suggested course of action. If R0 resection is unattainable, treatment should
adhere to the guidelines for unresectable rectal cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Diagnosis: Histologically confirmed rectal adenocarcinoma. Preoperative Staging: Clinical
stages cT2-4aN0-2. Tumor Location: Tumor's lower edge within 8cm from the anus,
potentially affecting anal preservation or function.
Metastasis Screening: Preoperative chest, abdomen, and pelvis CT to rule out distant
metastasis.
Biomarkers: Positive expression of pMMR (MSH1/MSH2/MSH6/PMS2) on tumor biopsy
immunohistochemistry.
Staging Methods: Combination of thoracic and abdominal pelvic CT, pelvic MRI, and
endoscopic or transrectal ultrasound.
Patient Characteristics Age: 18 to 70 years. Performance Status: ECOG score of 0-1. Life
Expectancy: At least 2 years. Blood Counts: WBC >4000/mm^3, PLT >100,000/mm^3, Hb >10g/dL
(chronic anemia with Hb < 10.0g/dL subject to multidisciplinary team review).
Liver Function: Serum total bilirubin ≤1.5×ULN (≤3×ULN for Gilbert syndrome); AST and ALT
≤2.5×ULN.
Renal Function: Serum creatinine ≤1.5×ULN or creatinine clearance >50 mL/min. Other
Criteria: Non-pregnant, not nursing, no other malignancies (except non-melanoma skin
cancer or cervical carcinoma in situ) within the past 5 years, capable of providing
informed consent, no severe comorbidities affecting survival.
Prior Treatment No prior surgery, chemotherapy, or radiotherapy for rectal cancer. No
prior biological therapy. No restrictions on previous endocrine therapy.
Exclusion Criteria:
Informed Consent: Lack of signed informed consent. Genetic Markers: Tumor biopsy
indicating dMMR or MSI-H detected. Advanced Tumor Stage: Preoperative assessment showing
tumor invasion of surrounding tissues/organs (T4b).
Obstruction: Unresolved colonic obstruction; presence of tumor perforation. Metastasis:
Evidence of preoperative distant metastasis. Cardiac Conditions: Arrhythmia requiring
antiarrhythmic therapy (excluding beta-blockers or digoxin), symptomatic coronary artery
disease or recent myocardial ischemia (within 6 months), or congestive heart failure
above NYHA Grade II.
Hypertension: Severe, poorly controlled hypertension. Infections: HIV infection, active
chronic hepatitis B or C, other serious infections; active tuberculosis or anti-TB
therapy within the past year.
Organ Function: Poor fluid quality, organ function decompensation. Previous Treatment:
History of pelvic or abdominal radiotherapy; multiple primary colorectal cancers.
Neurological Conditions: Seizures requiring management (e.g., steroids, antiepileptic
therapy).
Cancer History: Other malignant tumors within the past 5 years, excluding cured cervical
carcinoma in situ or basal cell carcinoma of the skin.
Substance Abuse: Substance abuse or medical, psychological, or social conditions
affecting study participation or result evaluation.
Allergies: Known or suspected allergy to study drugs or related medications. Stability:
Any unstable condition that may compromise safety or compliance. Reproductive Status:
Pregnant or lactating women, or fertile women not using effective contraception.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
651 Dongfeng Road East
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Peirong Ding, Doctor
Phone:
13543478645
Phone ext:
+86
Email:
dingpr@sysucc.org.cn
Contact backup:
Last name:
Kai Han, Doctor
Phone:
18602042643
Phone ext:
+86
Email:
hankai@sysucc.org.cn
Start date:
December 12, 2022
Completion date:
December 2025
Lead sponsor:
Agency:
Pei-Rong Ding
Agency class:
Other
Collaborator:
Agency:
Yunnan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Liaoning Tumor Hospital & Institute
Agency class:
Other
Collaborator:
Agency:
Shantou Central Hospital
Agency class:
Other
Collaborator:
Agency:
Fujian Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Jiangsu Provincial People's Hospital
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06417476
