Clinical trial NCT04103697: Neoadjuvant Chemotherapy in Patients With Intermediate Risk Upper and Mid Rectal Cancer
Official title: A Multicenter Prospective Phase III Clinical Trial of Neoadjuvant CapOx Chemotherapy in Patients With Intermediate Risk Middle and Upper Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Neoplasms Malignant
Rectum Carcinoma
Rectal Cancer
Keywords: rectal cancer
neoadjuvant chemotherapy
mesorectal excision
Lead sponsor: Blokhin's Russian Cancer Research Center
Sponsor class: OTHER
First posted: 2019-09-25
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 4 cycles of neoadjuvant CapOx chemotherapy is more effective than the upfront surgery in patients with intermediate risk CRM"-" mid and upper rectal cancer.

Detailed description: This trial aims to investigate the efficacy of neoadjuvant chemotherapy compared to upfront surgery in intermediate risk rectal cancer patients. This is a prospective multicenter open-label 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 and surgery or surgery alone. A stratification will be performed based on N stage, tumor location in the middle or upper rectum and clinical center. Patients with cT3-4aN1-2M0, T4aN0M0 cancer in the upper rectum and сТ2-Т3bN1M0 (based on preoperative MRI) cancer in the middle rectum are included. All patients are potential candidates for adjuvant chemotherapy, according to preoperative staging. 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 decision to proceed with adjuvant chemotherapy postoperatively will be based on pTNM stage in both treatment arms, according to actual treatment guidelines. The target accrual is 280 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 10% 3-yr disease-free survival (75% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging before and after neoadjuvant chemotherapy and before surgery. Pelvic MRI isbject 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
* cT3-4aN1-2M0 cancer of the upper rectum or сТ2-Т3bN1M0 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

Primary outcomes:
measure: 3-year disease-free survival
timeFrame: 3 years
Secondary outcomes:
measure: Adjuvant chemotherapy compliance
timeFrame: 6 months
measure: Acute chemotherapy toxicity
timeFrame: 14 weeks
measure: pathologic complete response rate (pCR)
timeFrame: 1 month
measure: local recurrence rate
timeFrame: 3 years
measure: 3-year overall survival
timeFrame: 3 years
measure: Operative morbidity
timeFrame: 30 days
measure: Neoadjuvant chemotherapy disease progression rate
timeFrame: 14 weeks
measure: Preoperative tumor-associated complications rate
timeFrame: 14 weeks
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: