Consolidation Chemotherapy for Locally Advanced Mid or Low Rectal Cancer After Neoadjuvant Concurrent Chemoradiotherapy

Rectal Cancer Clinical Trial

Official title:

KCSP Trial of cONsolidation Chemotherapy for Locally Advanced Mid or Low Rectal Cancer After neoadjUvant Concurrent chemoraDiothErapy: A Multicenter, Randomized Controlled Trial (KONCLUDE Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02843191
• Other study ID #: KSCP2016
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: July 31, 2024

Study information

• Verified date: March 2023
• Source: Kyung Hee University Hospital at Gangdong
• Contact: Suk-Hwan Lee, MD, PhD
• Phone: +82-2-440-7044
• Email: leeshdr[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is to assess the efficacy and feasibility of consolidation chemotherapy after neoadjuvant chemoradiotherapy for locally advanced mid or low rectal cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 358
• Est. completion date: July 31, 2024
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of mid or low rectum

2. Locally advanced rectal cancer confirmed by image (i.e. Magnetic resonance image)

• Clinical stage T1-3N1or2 on MRI

• Clinical stage cT3N0 (or depth of perirectal invasion by tumor >5mm on MRI)

• Suspicious of circumferential invasion on MRI (or circumferential margin <1mm)

3. ECOG performance status of 0-2

4. ASA grade = 3

5. An informed consent has been signed by the patient

Exclusion Criteria:

1. Upper rectal cancer

2. Clinical stage T1or2N0 on MRI

3. Clinical stage T4Nany on MRI

4. Clinical stage TanyNanyM1 by image or histology

5. The patient received chemotherapy or radiotherapy during the past 6 months

6. The patient received any therapy for colorectal cancer or another malignancy during the past 5 years

7. The patient has severe underlying diseases or poor condition to receive chemotherapy or radiotherapy

8. Pregnant of breastfeeding women

9. The patient who participate in another clinical trial, or receives any drug for the trial

10. Uncontrolled peripheral neuropathy (more than grade 2)

11. Any unhealed wound, fracture, peptic ulcer, or intraabdominal abscess

12. Active gastrointestinal bleeding

13. Patients with an active infection, which needs antibiotic therapy, during the randomization period

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Chemotherapy
5-FU, Leucovorin, and Oxaliplatin (FOLFOX regimen)

Locations

Country	Name	City	State
Korea, Republic of	Inje University Busan Paik hospital	Busan
Korea, Republic of	Chuncheon Sacred Heart Hospital, Hallym University College of Medicine	Chuncheon
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Wonkwang University Hospital	Iksan
Korea, Republic of	Gangnam Severance Hospital, Yonsei University College of Medicine	Seoul
Korea, Republic of	Inje University Sanggye Paik Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital, The Catholic University College of Medicine	Seoul
Korea, Republic of	Ajou University School of Medicine	Suwon
Korea, Republic of	Uijeongbu St. Mary's Hospital, The Catholic University College of Medicine	Uijeongbu
Korea, Republic of	Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine	Wonju
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan

Sponsors (2)

Lead Sponsor	Collaborator
Kyung Hee University Hospital at Gangdong	Korean Society of ColoProctology

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (25)

Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. doi: 10.1200/JCO.2010.34.4911. Epub 2011 May 23. — View Citation

Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829. Erratum In: N Engl J Med. 2007 Aug 16;357(7):728. — View Citation

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. — View Citation

Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19-23. doi: 10.1007/s003840050072. — View Citation

Gao YH, Lin JZ, An X, Luo JL, Cai MY, Cai PQ, Kong LH, Liu GC, Tang JH, Chen G, Pan ZZ, Ding PR. Neoadjuvant sandwich treatment with oxaliplatin and capecitabine administered prior to, concurrently with, and following radiation therapy in locally advanced rectal cancer: a prospective phase 2 trial. Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1153-60. doi: 10.1016/j.ijrobp.2014.07.021. Epub 2014 Oct 13. — View Citation

Garcia-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum. 2003 Mar;46(3):298-304. doi: 10.1007/s10350-004-6545-x. — View Citation

Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM; Timing of Rectal Cancer Response to Chemoradiation Consortium. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011 Jul;254(1):97-102. doi: 10.1097/SLA.0b013e3182196e1f. — View Citation

Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. 1985 Jun 6;312(23):1465-72. doi: 10.1056/NEJM198506063122301. — View Citation

Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Seitz JF, Bedenne L, Juzyna B, Conroy T. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012 Dec 20;30(36):4558-65. doi: 10.1200/JCO.2012.42.8771. Epub 2012 Oct 29. — View Citation

Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. doi: 10.1200/JCO.2009.25.8376. Epub 2010 Mar 1. — View Citation

Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629. — View Citation

Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2. — View Citation

Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. doi: 10.1016/S1470-2045(14)70377-8. Epub 2014 Sep 4. — View Citation

Kapiteijn E, Kranenbarg EK, Steup WH, Taat CW, Rutten HJ, Wiggers T, van Krieken JH, Hermans J, Leer JW, van de Velde CJ. Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective randomised trial with standard operative and histopathological techniques. Dutch ColoRectal Cancer Group. Eur J Surg. 1999 May;165(5):410-20. doi: 10.1080/110241599750006613. — View Citation

Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. doi: 10.1056/NEJMoa010580. — View Citation

Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994 Jun 1;73(11):2680-6. doi: 10.1002/1097-0142(19940601)73:113.0.co;2-c. — View Citation

Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. doi: 10.1200/JCO.2012.42.9597. Epub 2012 Sep 24. Erratum In: J Clin Oncol. 2013 Jan 20;31(3):399. — View Citation

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. — View Citation

Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Strobel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. doi: 10.1016/S1470-2045(15)00159-X. Epub 2015 Jul 15. — View Citation

Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005 Dec 1;23(34):8688-96. doi: 10.1200/JCO.2005.02.1329. Epub 2005 Oct 24. — View Citation

Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009 Nov 1;27(31):5124-30. doi: 10.1200/JCO.2009.22.0467. Epub 2009 Sep 21. — View Citation

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. doi: 10.1056/NEJMoa040694. — View Citation

Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rodel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. doi: 10.1200/JCO.2011.40.1836. Epub 2012 Apr 23. — View Citation

Valentini V, Coco C, Picciocchi A, Morganti AG, Trodella L, Ciabattoni A, Cellini F, Barbaro B, Cogliandolo S, Nuzzo G, Doglietto GB, Ambesi-Impiombato F, Cosimelli M. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys. 2002 Jul 1;53(3):664-74. doi: 10.1016/s0360-3016(02)02764-5. — View Citation

van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	The rates of patients who survive without recurrence	3 years
Primary	Pathologic complete response	Pathologic complete response is defined as no residual tumor on the surgical specimen after chemoradiotherapy. (i.e. Mandard grade 1 or Dworak grade 4)	2 years
Secondary	Radiotherapy-related complications	Complications according to the CTCAE 4.0	2 years
Secondary	R0 resection	R0 resection is defined as resection without remnant tumor, whereas R1 resection as microscopic residual tumor and R2 resection as gross residual tumor. R0 resection will be proven histologically as no resection margin involvement of tumor.	2 years
Secondary	Tumor response rate	Amount of tumor regression after surgery according to the guideline including Mandard or Dworak	2 years
Secondary	Postoperative complications	Complications after surgery	2 years
Secondary	Peripheral neuropathy	Peripheral neuropathy will be evaluated as grade 1 to 4 according to NCI CTCAE 4.0.	3 years