Clinical trial NCT02288195: CONVERT: Neoadjuvant Chemotherapy Alone Versus Preoperative Chemoradiation for Locally Advanced Rectal Cancer Patients
Official title: Phase III Study of Neoadjuvant Chemotherapy With Capecitabine and Oxaliplatin Versus Chemoradiation for Locally Advanced Rectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Neoplasms
Keywords: Neoadjuvant Chemotherapy
Preoperative radiotherapy
Chemoradiotherapy
Capecitabine
Oxaliplatin
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Shantou Central Hospital
name: Liaoning Cancer Hospital & Institute
name: The First Affiliated Hospital with Nanjing Medical University
name: Fujian Cancer Hospital
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: First Affiliated Hospital of Chongqing Medical University
name: The First Affiliated Hospital of Guangzhou Medical University
name: Guangdong Provincial People's Hospital
name: Cancer Hospital of Guangxi Medical University
name: Meizhou People's Hospital
name: Henan Cancer Hospital
name: Affiliated Cancer Hospital of Shantou University Medical College
name: Hubei Cancer Hospital
name: First Affiliated Hospital of Kunming Medical University
name: Longyan City First Hospital
name: Shengjing Hospital
name: Zhejiang Cancer Hospital
name: Jiangmen Central Hospital
name: West China Hospital
name: The Third Affiliated Hospital of Kunming Medical College.
First posted: 2014-11-11
Enrollment: 663
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Although neoadjuvant radiotherapy greatly decreases local recurrence in locally advanced rectal cancer patients undergoing surgery, it inevitably results in short-term and long-term toxicities. More importantly, it has not been confirmed that neoadjuvant radiotherapy could improve overall survival. The purpose of this study is to compare the effects of chemotherapy alone using a combination regimen known as XELOX (capecitabine and oxaliplatin ) and selective use of the standard treatment to the standard treatment of chemotherapy and radiation.

Detailed description: This randomised, open-label, multicentre,phase 3 trial began in August, 2014, as an adjuvant trial comparing capecitabine-based neoadjuvant chemoradiotherapy with chemotherapy alone,in patients aged 18 years to 75 with clinical stage II-III locally advanced rectal cancer from six Chinese institutions.

Patients with local advanced rectal cancer (T2N+ or T3-4aNany,M0, CRM≥2mm, 12cm from the anus verge) were scheduled to Group A: receive neoadjuvant chemotherapy alone (4 cycles of XELOX: oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) followed by radical surgery and 4 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) and Group B :chemoradiotherapy (50.4 Gy plus capecitabine 1650 mg/m² administered orally and concurrently with radiation therapy for 5 days per week.) followed by radical surgery and 6 cycles of XELOX ( oxaliplatin 130mg/m2 day 1，capecitabine 2000mg/m2 days 1-14, repeated every 21 days) The primary endpoint was 3-year local recurrence free survival; analyses were done based on all patients with post-randomization data.

Eligibility criteria: Inclusion Criteria:

DISEASE CHARACTERISTICS:

* Diagnosis of rectal adenocarcinoma
* Radiologically measurable or clinically evaluable disease
* Tumor location within 12cm from anal verge
* Clinical stage T2N+ or T3-4aNany,M0 Clinical staging should be estimated based on the combination of the following assessments: physical examination by the primary surgeon, CT scan of the chest/abdomen/pelvis, and a pelvic MRI with or without an endorectal ultrasound (ERUS)
* No evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on pre-operative MRI
* No tumor causing symptomatic bowel obstruction
* No distant metastasis

PATIENT CHARACTERISTICS:

* ECOG performance status 0, 1
* White Blood Cell (WBC) ≥ 4,000/mm³
* Platelets ≥ 100,000/mm³
* Hemoglobin \> 10.0 g/dL
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST and ALT ≤ 1.5 times ULN
* Creatinine ≤ 1.5 times ULN
* No co-morbid illnesses or other concurrent disease that, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Exclusion Criteria:

* Pregnant or nursing
* Patient of child-bearing potential is not willing to employ adequate contraception
* Not willing to return to enrolling medical site for all study assessments
* With other invasive malignancy ≤ 5 years prior to registration; exceptions are colonic polyps, non-melanoma skin cancer, or carcinoma-in-situ of the cervix
* Chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years)
* Prior pelvic radiation

Primary outcomes:
measure: Local-regional failure-free survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Disease free survival
timeFrame: Up to 5 years
measure: Pathologic complete response and tumor regression grade
timeFrame: Up to 18 weeks
measure: Pelvic R0 resection rate
timeFrame: Up to 18 weeks
measure: Overall survival
timeFrame: Up to 5 years
measure: Adverse event (AE) profiles
timeFrame: Up to 5 years
measure: Rate of receiving pre-operative or post-operative chemoradiation
timeFrame: Up to 30 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University, Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Peirong Ding, MD, Ph D
role: STUDY_CHAIR
References:
citation: Mei WJ, Wang XZ, Li YF, Sun YM, Yang CK, Lin JZ, Wu ZG, Zhang R, Wang W, Li Y, Zhuang YZ, Lei J, Wan XB, Ren YK, Cheng Y, Li WL, Wang ZQ, Xu DB, Mo XW, Ju HX, Ye SW, Zhao JL, Zhang H, Gao YH, Zeng ZF, Xiao WW, Zhang XP, Zhang X, Xie E, Feng YF, Tang JH, Wu XJ, Chen G, Li LR, Lu ZH, Wan DS, Bei JX, Pan ZZ, Ding PR. Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial. Ann Surg. 2023 Apr 1;277(4):557-564. doi: 10.1097/SLA.0000000000005780. Epub 2022 Dec 20.