Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neoadjuvant chemotherapy | Experimental | Patients will receive 4 cycles of neoadjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). In case of partial response or stable disease (based on pelvic MRI) patients proceed to surgery within 2 weeks. In case of disease progression patients receive 50 Gy pelvic chemoradiotherapy with capecitabine 825 mg/m2 bid per os on radiation days and then surgery following 8-10 weeks. After surgery patients receive 4 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). |
|
| Neoadjuvant radiotherapy | Active Comparator | Patients will receive 5x5 Gy radiotherapy and then surgery following 6-8 weeks. After surgery patients receive 8 cycles of adjuvant CapOx chemotherapy (oxaliplatin 130 mg/m2 iv day 1, capecitabine 2000 mg/m2 bid per os days 1-14 every 3 weeks). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capecitabine | Drug | 2000 mg/m2, bid, per os, days 1-14, 4 cycles |
|
| Measure | Description | Time Frame |
|---|---|---|
| 2-year local recurrence rate | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Adjuvant chemotherapy compliance | Proportion of patients who receive a complete course of adjuvant chemotherapy | 6 months |
| Acute chemotherapy toxicity | Toxicity measured according to NCI-CTCAE v.5.0 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Zaman Z Mamedli, PhD | N.N.Blokhin Russian Cancer Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| N.N.Blokhin Russian Cancer Research Center | Moscow | 115478 | Russia |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| D000077150 | Oxaliplatin |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Oxaliplatin | Drug | 130 mg/m2 iv day 1, 4 cycles |
|
| Capecitabine | Drug | 825 mg/m2, bid, per os, only on days of radiation (Monday through Friday) |
|
|
| Radiotherapy | Radiation | Pelvic radiotherapy dose: 44 Gy on regional nodes, 50 Gy on primary tumor |
|
| Rectal cancer surgery | Procedure | Laparoscopic or open total mesorectal excision |
|
| Radiotherapy | Radiation | Pelvic radiotherapy dose: 25 Gy in 5 Gy fractions |
|
| 6 months |
| pathologic complete response rate (pCR) | 1 month |
| 2-year overall survival | 2 years |
| 2-year disease-free survival | 2 years |
| Operative morbidity | Morbidity measured according to Clavien-Dindo classification | 30 days |
| Neoadjuvant chemotherapy disease progression rate | Proportion of patients with disease progression during neoadjuvant chemotherapy | 3 months |
| Preoperative tumor-associated complications rate | The rate of tumor-associated complications (bowel obastruction, bleeding etc) during neoadjuvant chemotherapy | 3 months |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D013812 | Therapeutics |