Clinical trial NCT00833131: The Randomised Study of Preoperative Radiotherapy With Consolidating Chemotherapy for Unresectable Rectal Cancer
Official title: Short-course Preoperative Radiotherapy With Consolidating Chemotherapy vs. Preoperative Chemoradiation in Patients With Unresectable Rectal Cancer: Phase III Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Cancer
Keywords: Rectal cancer
Preoperative radiotherapy and consolidating chemotherapy
Lead sponsor: Polish Colorectal Cancer Study Group
Sponsor class: NETWORK
Collaborators: name: Maria Sklodowska-Curie National Research Institute of Oncology
name: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow
name: Poznan University of Medical Sciences
name: Medical University of Lublin
First posted: 2009-01-30
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The rate of patients with R0 resection
timeFrame: Surrogate endpoint available immediatly after surgery
Secondary outcomes:
measure: Overall long-term survival
timeFrame: 5 years
measure: Progression-free long-term survival
timeFrame: 5 years
measure: The rate of local failures
timeFrame: 5 years
measure: The rate of distant metastases
timeFrame: 5 years
measure: The rate of early toxicity of neoadjuvant treatment according to the NCI CTCAE (version 3.0)
timeFrame: 3 months
measure: The rate of postoperative complications
timeFrame: 30 days
measure: The rate of late toxicity according to the RTOG/EORTC scale
timeFrame: 5 years
measure: The rate of complete pathological response
timeFrame: Surrogate endpoint available immediatly after surgery
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: M. Sklodowska-Curie Memorial Cancer Centre
Study officials:
affiliation: Roentgena 5, 02-781 Warsaw, Poland
name: Krzysztof Bujko, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.