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

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

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.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Radiation: Short course of radiotherapy; Radiation: Radiochemotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 540
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 02-781
    • Recruiting
    • M. Sklodowska-Curie Memorial Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; 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; 5 x 5 Gy and afer one week interval consolidating chemotherapy of 3 courses of FOLFOX4; Other Names: short radiation; consolidating chemotherapy
ACTIVE_COMPARATOR: 2; 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; 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.; Other Names: chemoradiation

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Polish Colorectal Cancer Study Group
• Collaborators: Poznan University of Medical Sciences; Medical University of Lublin; Maria Sklodowska-Curie National Research Institute of Oncology; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow

Publications and helpful links

General Publications

• Bujko K, Kolodziejczyk M. The 5 x 5 Gy with delayed surgery in non-resectable rectal cancer: a new treatment option. Radiother Oncol. 2008 Jun;87(3):311-3. doi: 10.1016/j.radonc.2007.12.020. Epub 2008 Jan 18. No abstract available.
• Cisel B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spalek M, Polkowski W, Jankiewicz M, Stylinski R, Bebenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Zelazowska-Omiotek U, Kepka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kladny J, Majewski A, Kapuscinski W, Suwinski R, Bujko K; Polish Colorectal Study Group. Long-course preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019 Aug 1;30(8):1298-1303. doi: 10.1093/annonc/mdz186.
• Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Krynski J, Michalski W, Oledzki J, Kusnierz J, Zajac L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwolinski J, Winiarek M, Wisniowska K, Partycki M, Beczkowska K, Polkowski W, Stylinski R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Cisel B, Skorzewska M, Mielko J, Bebenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac L, Wojnar A, Lesniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kolodziejski L, Radkowski A, Zelazowska-Omiotek U, Czeremszynska B, Kepka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopylo R, Markiewicz W, Kedzierawski P, Wydmanski J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. doi: 10.1093/annonc/mdw062. Epub 2016 Feb 15.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (ANTICIPATED): November 1, 2012
• Study Completion (ANTICIPATED): November 1, 2015

Study Registration Dates

• First Submitted: January 29, 2009
• First Submitted That Met QC Criteria: January 29, 2009
• First Posted (ESTIMATE): January 30, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2010
• Last Update Submitted That Met QC Criteria: April 14, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Rectal cancer; Preoperative radiotherapy and consolidating chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: PGBRJG0109