NCT02000050

Phase II Study of Up-front Chemotherapy and Neo-adjuvant Short-course Radiotherapy for Resectable Rectal Carcinoma (COLORE)

Phase II Study of Up-front Chemotherapy and Neo-adjuvant Short-course Radiotherapy for Resectable Rectal Carcinoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Phase II study of up-front chemotherapy and neo-adjuvant shortcourse radiotherapy for resectable rectal carcinoma. Study Design: Phase II, open-label, single-arm, multi-centre study. STUDY PRODUCT,DOSE,ROUTE,REGIMEN AND DURATION OF ADMINISTRATION: 1. Neoadjuvant Treatment (pre-operative chemo-radiotherapy regimen): FOLFOX4\* 2 cycles (WK1+WK3) - Tomotherapy\*\* (WK5) - FOLFOX4\* 2 cycles (WK7+WK9) \* Oxaliplatin 85 mg/m2 iv: day 1 Levofolinate 100 mg/m2 iv: day 1-2 5-fluorouracil 400 mg/m2 iv in bolus and 600 mg/m2 iv infusion over 22h: day 1-2 Every cycle will last 2 weeks (approximately 48 hours of treatment infusion and 12 days of rest). \*\* 25 Gy in 5 consecutive fractions, one fraction per day in 5 days on CTV (Clinical Target Volume) at the isodose of the 95% of the total dose. The treatment plan will be elaborated at the work-station dedicated to the Helicoidal Tomotherapy. The treatment could be planned also with linear accelerator with IGRT-IMRT technique or VMAT technique. 2. Restaging (week 11) 3. Surgery (week 12-16) with Total Mesorectal Excision (TME) 4. End Of Treatment (week 16-32) 5. Adjuvant therapy (The maximum interval between surgery and start of adjuvant therapy should be 8 weeks): 6. FOLFOX4\* 8 cycles (every 2 weeks) Study Duration: about 5 years. Enrollment period: 36 months. Treatment period: about 8 months. Follow-up: 1 year. NUMBER OF SUBJECTs: · Step A: a maximum of 6 patients. 6 evaluable patients are needed to assess toxicity. If 1 toxicity resulting in discontinuation of treatment will be observed in 6 patients, the treatment can be considered safe (with a confidence \> 90%). If 2 or more toxicity resulting in discontinuation of treatment on 6 patients, the study will be stopped because not safe and another type of radiotherapy schedule must be designed. · Step B: a total of 50 patients is required to be recruited in 2 years (including patients enrolled in Step A). The goal is to achieve a proportion of at least 15% of patients with a complete pathological response with the new radiochemotherapeutic treatment.

Detailed description

Title: Phase II study of up-front chemotherapy and neo-adjuvant shortcourse radiotherapy for resectable rectal carcinoma. Short Title/Acronym: COLORE Protocol Code: IRST154.01 Phase: 2 Study Design: Phase II, open-label, single-arm, multi-centre study. STUDY PRODUCT,DOSE,ROUTE,REGIMEN AND DURATION OF ADMINISTRATION: 1. Neoadjuvant Treatment (pre-operative chemo-radiotherapy regimen): FOLFOX4\* 2 cycles (WK1+WK3) - Tomotherapy\*\* (WK5) - FOLFOX4\* 2 cycles (WK7+WK9) \* Oxaliplatin 85 mg/m2 iv: day 1 Levofolinate 100 mg/m2 iv: day 1-2 5-fluorouracil 400 mg/m2 iv in bolus and 600 mg/m2 iv infusion over 22h: day 1-2 Every cycle will last 2 weeks (approximately 48 hours of treatment infusion and 12 days of rest). \*\* 25 Gy in 5 consecutive fractions, one fraction per day in 5 days on CTV (Clinical Target Volume) at the isodose of the 95% of the total dose. The treatment plan will be elaborated at the work-station dedicated to the Helicoidal Tomotherapy. The treatment could be planned also with linear accelerator with IGRT-IMRT technique or VMAT technique. 2. Restaging (week 11) 3. Surgery (week 12-16) with Total Mesorectal Excision (TME) 4. End Of Treatment (week 16-32) 5. Adjuvant therapy (The maximum interval between surgery and start of adjuvant therapy should be 8 weeks): 6. FOLFOX4\* 8 cycles (every 2 weeks) Study Duration: about 5 years. Enrollment period: 36 months. Treatment period: about 8 months. Follow-up: 1 year. OBJECTIVES Primary objectives: Step A: to evaluate the feasibility and safety of the chemoradiotherapy regimen. Step B: to evaluate the proportion of patients with pathological complete remission after combined radio-chemotherapy. Secondary objectives (of Step B): * To evaluate the safety of the neo-adjuvant treatment * To determine pathological down-staging * To evaluate the rate of R0 resection * To evaluate the sphincter saving resection rate * To evaluate median disease free survival and overall survival * To evaluate the correlation between biomarker, pathological response and outcome (auxiliary\\subsidiary Biological Study) NUMBER OF SUBJECT: · Step A: a maximum of 6 patients. 6 evaluable patients are needed to assess toxicity. If 1 toxicity resulting in discontinuation of treatment will be observed in 6 patients, the treatment can be considered safe (with a confidence \> 90%). If 2 or more toxicity resulting in discontinuation of treatment on 6 patients, the study will be stopped because not safe and another type of radiotherapy schedule must be designed. · Step B: a total of 50 patients is required to be recruited in 2 years (including patients enrolled in Step A). The goal is to achieve a proportion of at least 15% of patients with a complete pathological response with the new radiochemotherapeutic treatment. STATISTICAL METHODOLOGY: The primary analysis will be performed on the ITT (Intention-To-Treat) population, while the secondary analysis will be conducted on the PP (Per Protocol) population. The number and percentage of treated patients undergoing grade 1 to 4 adverse events (CTC-AE, version 4.0) will be tabulated in the ITT and PP population. No statistical inference will be performed. Step A: Patients, tumor characteristics and toxicity events observed will be described. Step B: The proportion of patients with pathological Complete Response will be calculated. Safety profile will be analyzed. OS (Overall Survival) and DFS (Disease Free Survival) will be estimated with Kaplan-Meier method (Kaplan El, Meier P., J Am Stat Assoc 1958). No interim analysis will be performed. The 95% confidence intervals should also be provided.

Conditions

• Rectal Carcinoma

Interventions

Type	Name	Description
DRUG	FOLFOX4	FOLFOX4
RADIATION	Tomotherapy	Tomotherapy
PROCEDURE	TME (Total Mesorectal Excision)	TME (Total Mesorectal Excision)

Timeline

• Start date: 2013-10-11
• Primary completion: 2019-03-15
• Completion: 2019-03-15
• First posted: 2013-12-03
• Last updated: 2025-01-30

Locations

2 sites across 1 country: Italy