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

• ClinicalTrials.gov Identifier: NCT00833131
• Recruitment Status: Unknown
• First Posted: January 30, 2009
• Last Update Posted: April 15, 2010
• Sponsor: Polish Colorectal Cancer Study Group
• Collaborators: Maria Sklodowska-Curie National Research Institute of Oncology; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow; Poznan University of Medical Sciences; Medical University of Lublin
• Information provided by: Polish Colorectal Cancer Study Group

Tracking Information

• First Submitted Date: January 29, 2009
• First Posted Date: January 30, 2009
• Last Update Posted Date: April 15, 2010
• Study Start Date: November 2008
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 29, 2009): The rate of patients with R0 resection [ Time Frame: Surrogate endpoint available immediatly after surgery ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 29, 2009)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rectal Cancer

Intervention

• 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
• 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 Name: chemoradiation

Study Arms

• 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.
  Intervention: Radiation: Short course of radiotherapy
• 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.
  Intervention: Radiation: Radiochemotherapy

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 29, 2009): 540
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2015
• Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT00833131
• Other Study ID Numbers: PGBRJG0109
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prof. Marek P. Nowacki, Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology in Warsaw
• Original Responsible Party: Same as current
• Current Study Sponsor: Polish Colorectal Cancer Study Group
• Original Study Sponsor: Same as current

Collaborators

• Maria Sklodowska-Curie National Research Institute of Oncology
• Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Cracow
• Poznan University of Medical Sciences
• Medical University of Lublin

Investigators

• Principal Investigator: Krzysztof Bujko, Prof.; Roentgena 5, 02-781 Warsaw, Poland

• PRS Account: Polish Colorectal Cancer Study Group
• Verification Date: April 2010