Neo-adjuvant Short Course Chemo-radiation Therapy in Locally Advanced Rectal Cancer Patients

NCT ID: NCT04370418

Last Updated: 2022-02-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2023-09-30

Brief Summary

• The primary objective of this trial is to assess the safety and feasibility of 5-FU when given concurrently with5 Gy x 5 fractions IMRT.
• The secondary endpoint is to assess disease local control and the response rate after short course radiotherapy concurrent with dose escalation infusion 5-fu followed by mFOLFOX and delayed surgery.

Detailed Description

Neo-adjuvant radiotherapy is associated with the improvement of local control for rectal cancer. For locally advanced stage II-III resectable rectal cancer, either preoperative short-course radiotherapy of 25 Gy in 5 consecutive days or long-course chemo-radiotherapy followed by radical Total Meso-rectal Excision is recommended. The Swedish Rectal Cancer Trial has demonstrated the lower rate of early toxicity of short course radiotherapy when compared to chemo-radiation. Short-course irradiation reduced the risk of local recurrence with evidence of overall survival improvement. Short-course regimen is less expensive and more convenient, especially in centers with long waiting lists. Two meta-analyses showed that short course is as effective as long course chemo-radiation in the management of locally advanced rectal cancer in the terms of sphincter preservation rates, down-staging, R0 resection, local control, and grade 3-4 toxicity. Despite reduction in local-regional recurrence risk with neo-adjuvant short course radiotherapy, distant disease recurrence remains a substantial risk for patients with locally advanced disease. In a controlled randomized trial, a short course radiotherapy followed by consolidation chemotherapy prior to surgery yielded superior overall survival outcomes compared to chemo-radiotherapy, without significant differences in disease-free survival, nor local or distant disease control rates. The phase III RAPIDO and STELLAR clinical trials are also evaluating short course radiotherapy and consolidation chemotherapy. The Stockholm III trial was a 3-arm trial that compared short-course RT with the standard 1-week delay to surgery, short-course RT with a 4- to 6-week delay to surgery, and long-course chemoradiation with a 4- to 6-week delay to surgery. The results show similar outcomes between the groups, but delaying the surgery after short-course RT decreased the rates of high-grade toxicity and allowed for an expedited treatment program.

Conditions

Neo-adjuvant Short Course Chemo-radiotherapy in Locally Advanced Cancer Rectum

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

neoadjuvant chemo-radiation

Short-course RT: 5 fractions of 5 Gy to a total dose of 25 Gy over 5 consecutive days. IMRT plans are generated with 6 MV photons.

Dose-escalated concurrent 5-FU: The 3 doses levels of 5-FU are 100, 150, and 200 mg/m2/d. 5-FU will be given by continuous infusion for 20 hours every day starting on the morning of radiation.

mFOLFOX: will be given 2 weeks after concurrent chemoradiation for a total of 4 cycles, with each cycle being 14 days. Surgery will be omitted in patients with complete pathological response and proceed to adjuvant chemotherapy. If patient develops progressive or metastatic disease, he/she will be omitted from the investigators study.

The surgery will be considered 4-8 weeks after end of therapy. Adjuvant mFOLFOX6: 6 cycles chemotherapy will begin between 4 weeks and 8 weeks after surgery.

Toxicities assessment: be using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Group Type: OTHER

short course chemo-radiation with 5-fluorouracil

Intervention Type: DRUG

neo-adjuvant short course chemo-radiation in locally advanced rectal cancer patients followed by delayed surgery

Interventions

short course chemo-radiation with 5-fluorouracil

neo-adjuvant short course chemo-radiation in locally advanced rectal cancer patients followed by delayed surgery

Intervention Type: DRUG

Other Intervention Names

5-fu

Eligibility Criteria

Inclusion Criteria

• Pathological confirmed cancer rectum
• Age between 20-80
• Clinical T3\4 or node positive disease by MRI

Exclusion Criteria

• Early stage cancer rectum
• M1 disease confirmed by imaging or pathological

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Mariam Mohsen Khalil

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

taha z mohran, professor

Role: STUDY_DIRECTOR

Assiut University

Locations

Assiut University

Asyut, Assuit, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

mariam m khalil, MD

Role: CONTACT

mariammohsenkhalil@aun.edu.eg

+201223117062

abeer f amin, professor

Role: CONTACT

abeeramin210@yahoo.com

Facility Contacts

Mariam M Khalil, master

Role: primary

mariammohsenkhalil@aun.edu.eg

+201223117062

References

Trakarnsanga A, Ithimakin S, Weiser MR. Treatment of locally advanced rectal cancer: controversies and questions. World J Gastroenterol. 2012 Oct 21;18(39):5521-32. doi: 10.3748/wjg.v18.i39.5521.

Reference Type: BACKGROUND

PMID: 23112544 (View on PubMed)

Swedish Rectal Cancer Trial; Cedermark B, Dahlberg M, Glimelius B, Pahlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. doi: 10.1056/NEJM199704033361402.

Reference Type: BACKGROUND

PMID: 9091798 (View on PubMed)

Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006 Oct;93(10):1215-23. doi: 10.1002/bjs.5506.

Reference Type: BACKGROUND

PMID: 16983741 (View on PubMed)

Zhou ZR, Liu SX, Zhang TS, Chen LX, Xia J, Hu ZD, Li B. Short-course preoperative radiotherapy with immediate surgery versus long-course chemoradiation with delayed surgery in the treatment of rectal cancer: a systematic review and meta-analysis. Surg Oncol. 2014 Dec;23(4):211-21. doi: 10.1016/j.suronc.2014.10.003. Epub 2014 Oct 29.

Reference Type: BACKGROUND

PMID: 25466851 (View on PubMed)

Kairevice L, Latkauskas T, Tamelis A, Petrauskas A, Pauzas H, Zvirblis T, Jarusevicius L, Saladzinskas Z, Pavalkis D, Janciauskiene R. Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus short-course radiotherapy without adjuvant chemotherapy both with delayed surgery for stage II-III resectable rectal cancer: 5-Year survival data of a randomized controlled trial. Medicina (Kaunas). 2017;53(3):150-158. doi: 10.1016/j.medici.2017.05.006. Epub 2017 Jun 22.

Reference Type: BACKGROUND

PMID: 28690144 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26884592 (View on PubMed)

Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial. BMC Cancer. 2013 Jun 7;13:279. doi: 10.1186/1471-2407-13-279.

Reference Type: BACKGROUND

PMID: 23742033 (View on PubMed)

J. Jin YT, S. Liu, Y. Zhu, W. Wang, G. Li, X. Wang, J. Wang, J. Yang, S. Li, N. Li, W. Liu, Y. Li, Y. Chi, A. Zhou, J. Huang, X. Wang, L. Jiang, J. Jiang, S. Zou. Short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR): a planned interim analysis. Annals of Oncology. 2018;29(suppl 8):167.

Reference Type: BACKGROUND

Erlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallbook O, Syk I, Glimelius B, Martling A. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017 Mar;18(3):336-346. doi: 10.1016/S1470-2045(17)30086-4. Epub 2017 Feb 10.

Reference Type: BACKGROUND

PMID: 28190762 (View on PubMed)

Wu H, Fang C, Huang L, Fan C, Wang C, Yang L, Li Y, Zhou Z. Short-course radiotherapy with immediate or delayed surgery in rectal cancer: A meta-analysis. Int J Surg. 2018 Aug;56:195-202. doi: 10.1016/j.ijsu.2018.05.031. Epub 2018 May 25.

Reference Type: BACKGROUND

PMID: 29807169 (View on PubMed)

Other Identifiers

short course chemoradiation

Identifier Type: -

Identifier Source: org_study_id