Clinical trial NCT04134897: Neoadjuvant Chemotherapy in Patients With Moderate Risk Mid Rectal Cancer
Official title: A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx in Patients With Intermediate Risk CRM-negative Middle Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Neoplasms Malignant
Rectum Carcinoma
Rectal Cancer
Keywords: rectal cancer
neoadjuvant chemotherapy
neoadjuvant radiotherapy
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2019-10-22
Enrollment: 316
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: The purpose of this study is to determine whether 3 months of neoadjuvant CapOx is non-inferior to neoadjuvant radiotherapy in patients with moderate risk CRM"-" mid rectal cancer.

Detailed description: This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to 5x5 Gy neoadjuvant radiotherapy in moderate risk CRM-negative rectal cancer patients. This is a prospective multicenter open-label non-inferiority randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either 4 cycles of neoadjuvant CapOx (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 per os bid days 1-14) chemotherapy, surgery and 4 cycles of adjuvant CapOx chemotherapy or 5x5 Gy radiotherapy, surgery and 8 cycles of adjuvant CapOx chemotherapy. A stratification will be performed based on сN stage and clinical center. Patients with сT3c-T3dN0-1M0, cT1-T3dN2M0 cancer in the middle rectum are included. Chemoradiotherapy (50 Gy with concomitant capecitabine 825 mg/m2 per os bid on radiation days) will be performed for patients with tumor progression after neoadjuvant chemotherapy. The main hypothesis is that the 2-year local recurrence rate is non-inferior after neoadjuvant chemotherapy and neoadjuvant radiotherapy in moderate risk mid rectal cancer patients. The target accrual is 158 patients in each treatment arm (including 10% potential data loss) based on non-recurrence rate of 98% in investigated and 96% in the control group with a non-inferiority margin of 3%, α=0,05, power 80%. An interim analysis is planned after 50% of the patients will reach a 2-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI is subject to central review. Conduction of this study and data collection are controlled by a local institutional board.

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Histologically verified colon rectal adenocarcinoma
* сT3c-T3dN0-1M0, cT1-T3dN2M0. cancer of the middle rectum (based on pelvic MRI)
* Tumor more than 2 mm from mesorectal fascia (based on pelvic MRI)
* Eastern Cooperative Oncology Group (ECOG) status 0-2
* Haemoglobin (HGB) \> 90 g/L
* Platelet Count (PLT) \> 120x10\*9/L
* Serum creatinine \< 150 µmol/L
* Total bilirubin \< 25 µmol/L

Exclusion Criteria:

* inability to obtain informed consent
* distant metastases
* synchronous or metachronous tumors
* previous chemotherapy or radiotherapy
* clinically significant cardiovascular disorders (myocardial infarction \< 6 months before visit, stroke \< \< 6 months before visit, instable angina \< 3 months before visit, arrhythmia, uncontrolled hypertension \> 160/100 mm hg
* clinically significant neurological disorders
* previous neuropathy 2 or higher
* current infection or heavy systemic disease
* pregnancy, breastfeeding
* ulcerative colitis
* individual intolerance to treatment components
* proven dihydropyrimidine dehydrogenase (DPD) deficiency
* participation in other clinical trials
* psychiatric disorders, which render patient unable to follow instructions or understand his/her condition
* technical inability to perform pelvic MRI
* inability of long-term followup of the patient
* HIV

Primary outcomes:
measure: 2-year local recurrence rate
timeFrame: 2 years
Secondary outcomes:
measure: Adjuvant chemotherapy compliance
timeFrame: 6 months
measure: Acute chemotherapy toxicity
timeFrame: 6 months
measure: pathologic complete response rate (pCR)
timeFrame: 1 month
measure: 2-year overall survival
timeFrame: 2 years
measure: 2-year disease-free survival
timeFrame: 2 years
measure: Operative morbidity
timeFrame: 30 days
measure: Neoadjuvant chemotherapy disease progression rate
timeFrame: 3 months
measure: Preoperative tumor-associated complications rate
timeFrame: 3 months
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: N.N.Blokhin Russian Cancer Research Center
Study officials:
affiliation: N.N.Blokhin Russian Cancer Research Center
name: Zaman Z Mamedli, PhD
role: PRINCIPAL_INVESTIGATOR
References: