The Randomised Study of Preoperative Radiotherapy With Consolidating Chemotherapy for Unresectable Rectal Cancer

Study Overview
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Brief Summary
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The addition of Oxaliplatin to conventionally fractionated chemoradiation (FULV or capecitabine) is considered as standard in unresectable rectal cancer by the panel of experts. The Investigators addressed the question whether short-course preoperative radiotherapy with consolidating chemotherapy of FOLFOX4 may increase the rate of R0 resection in patients with unresectable rectal cancer.

Detailed Description
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Patients with unresectable primary rectal cancer or with unresectable local recurrence without distant metastases are randomly allocated to control or experimental arm. The preoperative treatment in the control arm is conventionally fractionated chemoradiation with 50.4 Gy total dose in 28 fractions of 1.8 Gy over 5.5 weeks simultaneously with 5-Fu, leucovorin and oxaliplatin. Experimental group receive 25 Gy in 5 fractions of 5 Gy over 5 days and after one week interval - consolidating chemotherapy of 3 courses of FOLFOX4. Surgery should be curried out 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of fluorouracil or radiation. The study hypothesis is that the short-course preoperative radiotherapy with consolidating chemotherapy produce at least 10% increase of the rate of R0 resection compared to preoperative chemoradiation.

Official Title
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Short-course Preoperative Radiotherapy With Consolidating Chemotherapy vs. Preoperative Chemoradiation in Patients With Unresectable Rectal Cancer: Phase III Study

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: Short course of radiotherapy
* Radiation: Radiochemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable primary rectal cancer or with unresectable local recurrence without distant metastases. WHO performance status ≤ 2. Lower border of tumour ≤ 15 cm from anal verge. Exclusion Criteria: cardiac coronary arterial disease, arrhythmias, stroke even if they have occurred in the past and are controlled with medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>25 Gy in 5 fractions of 5 Gy over 5 days. One week interval. Consolidating chemotherapy of 3 courses of FOLFOX4. Surgery 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of fluorouracil. | Radiation: Short course of radiotherapy<br>* 5 x 5 Gy and afer one week interval consolidating chemotherapy of 3 courses of FOLFOX4<br>* Other names: consolidating chemotherapy;|
| Active Comparator: 2<br>Conventionally fractionated chemoradiation with 50.4 Gy total dose in 28 fractions of 1.8 Gy over 5.5 weeks. Surgery 10-11 weeks from beginning of radiation and at least 4 weeks from the last dose of radiation. | Radiation: Radiochemotherapy<br>* 28 x 1,8 Gy with simultaneous neoadjuvant chemotherapy: two courses of 5-Fu 325 mg/m2/day i.v. bolus and LV 20 mg/m2/day i.v.-bolus over 5 days given during 1-5 and 29-33 days of radiation. Oxaliplatin is given 50 mg/m2 once a week 5 times during 1, 8, 15, 22 and 29 days of radiation.<br>* Other names: chemoradiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of patients with R0 resection |  | Surrogate endpoint available immediatly after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall long-term survival |  | 5 years | 
| Progression-free long-term survival |  | 5 years | 
| The rate of local failures |  | 5 years | 
| The rate of distant metastases |  | 5 years | 
| The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 3.0) |  | 3 months | 
| The rate of postoperative complications |  | 30 days | 
| The rate of late toxicity according to the RTOG/EORTC scale |  | 5 years | 
| The rate of complete pathological response |  | Surrogate endpoint available immediatly after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Preoperative radiotherapy and consolidating chemotherapy