Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy for Rectal Cancer: A Randomized Controlled Trial

NCT05496491 | Recruiting

• 1 other identifier: NCCCRC
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this protocol is to compare neoadjuvant chemoradiation plus consolidation chemotherapy before surgical resection with the standard neoadjuvant chemoradiation followed by surgical resection and adjuvant chemotherapy in patients with rectal cancer.

Conditions

Rectal Neoplasms

Keywords

rectal; cancer; neoadjuvant; radiotherapy; chemotherapy; mesorectal; excision

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  Occurence of Disease Free Survival. If such an episode occurs, then it will be defined as=1 'YES' If such an episode does not occur, then it will be defined as=0 'NO'

  3 years postoperatively

Secondary Outcomes (9)

• Complete Pathological Response

  1 month postoperatively

• Postoperative Complication

  1 month postoperatively

• Length of Hospital Stay

  Maximum time frame 39 days postoperatively

• Readmission

  1 month postoperatively

• Negative Resection Margin

  1 month postoperatively

Study Arms (2)

Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy

EXPERIMENTAL

The experimental group will receive the standard 5-week neoadjuvant chemoradiotherapy (CRT). Thereafter, all patients will commence consolidation chemotherapy. At the 6th week after the end of CRT, patients will undergo MRI re-staging: In case of non-response (mrTRG 5) they will be submitted immediately to surgery, and, subsequently, excluded from the trial. In case of response (mrTRG 2-4) they will receive consolidation chemotherapy for the whole waiting period between the end of CRT and surgery - 12 weeks.

Radiation: Neoadjuvant Chemoradiotherapy; Drug: Consolidation Chemotherapy

Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy

ACTIVE COMPARATOR

The control group will receive the standard 5-week neoadjuvant chemoradiotherapy regimen. Six weeks after completion the patient will be re-staged with rectal MRI and depending on the response will be operated (TME): immediately in case of non-response (mrTRG 5) or after an additional 6-week delay (overall 12 weeks after the end of chemoradiotherapy) in case of partial response (mrTRG 2-4). Adjuvant chemotherapy will be, also, administered.

Radiation: Neoadjuvant Chemoradiotherapy; Drug: Adjuvant Chemotherapy

Interventions

Neoadjuvant Chemoradiotherapy RADIATION

5-week neoadjuvant radiotherapy regimen (28 x 1.8 Gy) combined with Capecitabine (bid 800 mg/m2, twice daily, on days 1-33-38)

Also known as: nCRT

Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy; Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy

Adjuvant Chemotherapy DRUG

8 cycles of CAPOX (Capecitabine bid 1000 mg/m2, twice daily, day 1-14, every 3 weeks and Oxaliplatin 130 mg/m2, day 1, every 3 weeks) or alternatively, 12 cycles of folinate, fluorouracil and oxaliplatin (FOLFOX)

Also known as: AC

Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy

Consolidation Chemotherapy DRUG

CAPOX (Capecitabine bid1000 mg/m2 and Oxaliplatin 130 mg/m2, day 1, every 3 weeks) or alternatively FOLFOX

Also known as: CC

Neoadjuvant Chemoradiotherapy and Consolidation Chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed rectal adenocarcinoma
• cT3, cT4, threatened CRM / MRF, EMVI (+), ≥N1
• Multidisciplinary tumor board decision for neoadjuvant treatment
• Tumor distance from the anal verge \<15 cm based on endoscopy or magnetic resonance imaging
• Patient 18 to 80 years old
• General health condition status WHO 0-1
• Absence of co-morbidities that may affect treatment
• Neutrophils \>1,500 / mm3, platelets \>100,000 / mm3, hemoglobin\> 10 g / dL, normal creatinine, and creatinine clearance\> 50 mL / min
• Signed informed consent of the patient

You may not qualify if:

• Distant metastases
• Non-resectable cancer
• Contraindications for the administration of chemotherapy
• Previous pelvic radiotherapy or chemotherapy
• History of inflammatory bowel disorders
• History of angina, acute myocardial infarction or heart failure
• Active sepsis or systemic infection
• Untreated physical and mental disability
• Synchronous malignancy
• Pregnancy or breast-feeding
• Lack of compliance with the protocol process
• Non-granting of signed informed consent

Sponsors & Collaborators

• Larissa University Hospital: lead

Study Sites (1)

Department of Surgery, University Hospital of Larissa

Larissa, 41110, Greece

RECRUITING

Related Publications (22)

• Liu S, Jiang T, Xiao L, Yang S, Liu Q, Gao Y, Chen G, Xiao W. Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021 Sep;26(9):e1555-e1566. doi: 10.1002/onco.13824. Epub 2021 Jun 7.

  PMID: 33987952 BACKGROUND

• Kasi A, Abbasi S, Handa S, Al-Rajabi R, Saeed A, Baranda J, Sun W. Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Dec 1;3(12):e2030097. doi: 10.1001/jamanetworkopen.2020.30097.

  PMID: 33326026 BACKGROUND

• Sutera P, Solomina J, Wegner RE, Abel S, Monga D, Finley G, McCormick J, Kirichenko AV. Post-Operative Morbidity and Mortality Following Total Neoadjuvant Therapy Versus Conventional Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer. J Gastrointest Cancer. 2021 Sep;52(3):976-982. doi: 10.1007/s12029-020-00401-3.

  PMID: 32936391 BACKGROUND

• Chang H, Jiang W, Ye WJ, Tao YL, Wang QX, Xiao WW, Gao YH. Is long interval from neoadjuvant chemoradiotherapy to surgery optimal for rectal cancer in the era of intensity-modulated radiotherapy?: a prospective observational study. Onco Targets Ther. 2018 Sep 21;11:6129-6138. doi: 10.2147/OTT.S169985. eCollection 2018.

  PMID: 30288048 BACKGROUND

• Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. doi: 10.1016/S1470-2045(20)30555-6. Epub 2020 Dec 7.

  PMID: 33301740 BACKGROUND

• Giunta EF, Bregni G, Pretta A, Deleporte A, Liberale G, Bali AM, Moretti L, Troiani T, Ciardiello F, Hendlisz A, Sclafani F. Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials. Cancer Treat Rev. 2021 May;96:102177. doi: 10.1016/j.ctrv.2021.102177. Epub 2021 Mar 16.

  PMID: 33798955 BACKGROUND

• Shi DD, Mamon HJ. Playing With Dynamite? A Cautious Assessment of TNT. J Clin Oncol. 2021 Jan 10;39(2):103-106. doi: 10.1200/JCO.20.02199. Epub 2020 Oct 14. No abstract available.

  PMID: 33052753 BACKGROUND

• Ludmir EB, Palta M, Willett CG, Czito BG. Total neoadjuvant therapy for rectal cancer: An emerging option. Cancer. 2017 May 1;123(9):1497-1506. doi: 10.1002/cncr.30600. Epub 2017 Mar 10.

  PMID: 28295220 BACKGROUND

• Petrelli F, Trevisan F, Cabiddu M, Sgroi G, Bruschieri L, Rausa E, Ghidini M, Turati L. Total Neoadjuvant Therapy in Rectal Cancer: A Systematic Review and Meta-analysis of Treatment Outcomes. Ann Surg. 2020 Mar;271(3):440-448. doi: 10.1097/SLA.0000000000003471.

  PMID: 31318794 BACKGROUND

• Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.

  PMID: 33862000 BACKGROUND

• Jimenez-Rodriguez RM, Quezada-Diaz F, Hameed I, Kalabin A, Patil S, Smith JJ, Garcia-Aguilar J. Organ Preservation in Patients with Rectal Cancer Treated with Total Neoadjuvant Therapy. Dis Colon Rectum. 2021 Dec 1;64(12):1463-1470. doi: 10.1097/DCR.0000000000002122.

  PMID: 34508014 BACKGROUND

• Bauer PS, Chapman WC Jr, Atallah C, Makhdoom BA, Damle A, Smith RK, Wise PE, Glasgow SC, Silviera ML, Hunt SR, Mutch MG. Perioperative Complications After Proctectomy for Rectal Cancer: Does Neoadjuvant Regimen Matter? Ann Surg. 2022 Feb 1;275(2):e428-e432. doi: 10.1097/SLA.0000000000003885.

  PMID: 32209914 BACKGROUND

• Sclafani F, Corro C, Koessler T. Debating Pros and Cons of Total Neoadjuvant Therapy in Rectal Cancer. Cancers (Basel). 2021 Dec 18;13(24):6361. doi: 10.3390/cancers13246361.

  PMID: 34944980 BACKGROUND

• Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, Safont MJ, Salud A, Vera R, Massuti B, Escudero P, Alonso V, Bosch C, Martin M, Minsky BD. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trialdagger. Ann Oncol. 2015 Aug;26(8):1722-8. doi: 10.1093/annonc/mdv223. Epub 2015 May 8.

  PMID: 25957330 BACKGROUND

• Marco MR, Zhou L, Patil S, Marcet JE, Varma MG, Oommen S, Cataldo PA, Hunt SR, Kumar A, Herzig DO, Fichera A, Polite BN, Hyman NH, Ternent CA, Stamos MJ, Pigazzi A, Dietz D, Yakunina Y, Pelossof R, Garcia-Aguilar J; Timing of Rectal Cancer Response to Chemoradiation Consortium. Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial. Dis Colon Rectum. 2018 Oct;61(10):1146-1155. doi: 10.1097/DCR.0000000000001207.

  PMID: 30192323 BACKGROUND

• Fang Y, Sheng C, Ding F, Zhao W, Guan G, Liu X. Adding Consolidation Capecitabine to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Propensity-Matched Comparative Study. Front Surg. 2022 Jan 27;8:770767. doi: 10.3389/fsurg.2021.770767. eCollection 2021.

  PMID: 35155545 BACKGROUND

• Chakrabarti D, Rajan S, Akhtar N, Qayoom S, Gupta S, Verma M, Srivastava K, Kumar V, Bhatt MLB, Gupta R. Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial. Br J Surg. 2021 May 27;108(5):511-520. doi: 10.1093/bjs/znab020.

  PMID: 33724296 BACKGROUND

• Wu H, Fan C, Fang C, Huang L, Li Y, Zhou Z. Preoperative short-course radiotherapy followed by consolidation chemotherapy for treatment with locally advanced rectal cancer: a meta-analysis. Radiat Oncol. 2022 Jan 24;17(1):14. doi: 10.1186/s13014-021-01974-4.

  PMID: 35073940 BACKGROUND

• Seo N, Kim H, Cho MS, Lim JS. Response Assessment with MRI after Chemoradiotherapy in Rectal Cancer: Current Evidences. Korean J Radiol. 2019 Jul;20(7):1003-1018. doi: 10.3348/kjr.2018.0611.

  PMID: 31270972 BACKGROUND

• Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.

  PMID: 19638912 BACKGROUND

• Chung F, Chan VW, Ong D. A post-anesthetic discharge scoring system for home readiness after ambulatory surgery. J Clin Anesth. 1995 Sep;7(6):500-6. doi: 10.1016/0952-8180(95)00130-a.

  PMID: 8534468 BACKGROUND

• Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, Rockall TA, Young-Fadok TM, Hill AG, Soop M, de Boer HD, Urman RD, Chang GJ, Fichera A, Kessler H, Grass F, Whang EE, Fawcett WJ, Carli F, Lobo DN, Rollins KE, Balfour A, Baldini G, Riedel B, Ljungqvist O. Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS(R)) Society Recommendations: 2018. World J Surg. 2019 Mar;43(3):659-695. doi: 10.1007/s00268-018-4844-y.

  PMID: 30426190 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms; Neoplasms

Interventions

Neoadjuvant Therapy; Chemotherapy, Adjuvant; Consolidation Chemotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Konstantinos Perivoliotis, MD

  University Hospital of Larissa

  PRINCIPAL INVESTIGATOR

• George Tzovaras, Prof

  University Hospital of Larissa

  STUDY DIRECTOR

Central Study Contacts

Konstantinos Perivoliotis, MD

CONTACT

2413501000; kperi19@gmail.com

George Tzovaras, Prof

CONTACT

2413502804; gtzovaras@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: There will be no blindness at the level of the patient, the treating physicians (surgeon, oncologist, radiotherapist) and the researcher who will record the data.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Perivoliotis Konstantinos, Principal Investigator

Model Details: The study will employ a prospective, parallel randomized-controlled design

Study Record Dates

• First Submitted: August 9, 2022
• First Posted: August 11, 2022
• Study Start: August 30, 2022
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)