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

Rectal Carcinoma Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma
• Rectal Carcinoma
• Rectal Neoplasms

• NCT number: NCT02000050
• Study type: Interventional
• Source: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Status: Completed
• Phase: Phase 2
• Start date: October 11, 2013
• Completion date: March 31, 2019