Adjuvant Treatment of Concurrent RT and CAPOX or Capecitabine Alone for Stage II and III Rectal Cancer

Rectal Neoplasms Clinical Trial

Official title:

Prospective Randomized Phase III Study of Concurrent Capecitabine and Radiotherapy With or Without Oxaliplatin as Adjuvant Treatment for Stage II and III Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00714077
• Other study ID #: CAMS_rectal cancer_01
• Status: Recruiting
• Phase: Phase 3
• First received: July 9, 2008
• Last updated: February 15, 2016
• Start date: April 2008
• Est. completion date: June 2018

Study information

• Verified date: February 2016
• Source: Chinese Academy of Medical Sciences
• Contact: Jing Jin, M.D.
• Phone: 861087788280
• Email: jingjin1025[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

The purpose of this study is:

• To compare the long-term of survival and local/regional control between the two postoperative concurrent chemoradiotherapy regimens: capecitabine vs. oxaliplatin and capecitabine,for stage II and III rectal cancer

• To compare the toxicity profile between the two different concurrent chemoradiotherapy regimens.

Description:

Adjuvant 5-FU based concurrent chemoradiotherapy and chemotherapy is the standard care for locally advanced stage II-III rectal cancer, based on several randomized Phase III clinical trials. With this standard treatment, 5-year local failure rate and distant metastasis rate is 10% and around 35%, respectively. Capecitabine, an analog of 5-fluoruracil (5FU), was demonstrated to have similar treatment results compared to 5-FU, but have much lower toxicities. Oxaliplatin based chemotherapy, also showed a better disease-free survival rate compared with 5-FU based-regimen. So far, some Phase I/II studies have shown the safety and preliminary results of either concurrent chemotherapy of capecitabine or oxaliplatin and capecitabine. The long-term results in comparison of capecitabine concurrent chemoradiotherapy with oxaliplatin/capecitabine concurrent chemoradiotherapy need to be further analyzed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 570
• Est. completion date: June 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 years old,male or female

• R0 surgery

• Pathologically approved as stage II or stage III

• Enrolled within 6 months from the date of surgery

• Upper border of tumor before surgery was under L5

• KPS>70% or ECOG 0-2

• No prior radiotherapy in the past 6 months

• Received chemotherapy no more than 4 cycles after surgery

• HGB>100 g/L, WBC=3.5x109 /L, PLT=100x109 /L; CR<1.5 x Upper normality,TB<2.5 X Upper normality,AST or ALT<2.5 x Upper normality,AKP<2.5 X Upper normality

• Signed consent

Exclusion Criteria:

• Other malignancies simultaneously except in situ cervix or nonmelanoma skin cancer

• Pregnancy or in lactation

• HGB<100 g/L, WBC<3.5x109 /L, PLT<100x109 /L; CR=1.5 x Upper normality,TB=2.5 X Upper normality,AST or ALT=2.5 x Upper normality,AKP=2.5 X Upper normality

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Rectal Neoplasms

Locations

Country	Name	City	State
China	Jing Jin	Beijing	Beijing
China	Jing Jin	Beijing	Beijing

Sponsors (8)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	Beijing Hospital, Cancer Hospital of Guizhou Province, General Hospital of Chinese Armed Police Forces, Hebei Medical University Fourth Hospital, Peking University Third Hospital, Shandong Cancer Hospital and Institute, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (27)

Adjuvant chemotherapy with oxaliplatin, in combination with fluorouracil plus leucovorin prolongs disease-free survival, but causes more adverse events in people with stage II or III colon cancer Abstracted from: Andre T, Boni C, Mounedji-Boudiaf L, et al. Multicenter international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer (MOSAIC) investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-51. Cancer Treat Rev. 2004 Dec;30(8):711-3. — View Citation

Cividalli A, Ceciarelli F, Livdi E, Altavista P, Cruciani G, Marchetti P, Danesi DT. Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule. Int J Radiat Oncol Biol Phys. 2002 Mar 15;52(4):1092-8. — View Citation

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. — View Citation

De Paoli A, Chiara S, Luppi G, Friso ML, Beretta GD, Del Prete S, Pasetto L, Santantonio M, Sarti E, Mantello G, Innocente R, Frustaci S, Corvò R, Rosso R. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol. 2006 Feb;17(2):246-51. Epub 2005 Nov 9. — View Citation

Dunst J, Reese T, Sutter T, Zühlke H, Hinke A, Kölling-Schlebusch K, Frings S. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol. 2002 Oct 1;20(19):3983-91. — View Citation

Fakih MG, Rajput A, Yang GY, Pendyala L, Toth K, Smith JL, Lawrence DD, Rustum YM. A Phase I study of weekly intravenous oxaliplatin in combination with oral daily capecitabine and radiation therapy in the neoadjuvant treatment of rectal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1462-70. Epub 2006 Jun 5. — View Citation

Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Lévi F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2000 Jan;18(1):136-47. — View Citation

Glynne-Jones R, Sebag-Montefiore D, Maughan TS, Falk SJ, McDonald AC. A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally advanced rectal cancer. Ann Oncol. 2006 Jan;17(1):50-6. Epub 2005 Nov 10. — View Citation

Gordon MA, Gil J, Lu B, Zhang W, Yang D, Yun J, Schneider S, Groshen S, Iqbal S, Press OA, Rhodes K, Lenz HJ. Genomic profiling associated with recurrence in patients with rectal cancer treated with chemoradiation. Pharmacogenomics. 2006 Jan;7(1):67-88. — View Citation

Jin J, Li YX, Liu YP, Wang WH, Song YW, Li T, Li N, Yu ZH, Liu XF. A phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):725-9. Epub 2005 Oct 19. — View Citation

Kim JC, Kim TW, Kim JH, Yu CS, Kim HC, Chang HM, Ryu MH, Park JH, Ahn SD, Lee SW, Shin SS, Kim JS, Choi EK. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):346-53. — View Citation

Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991 Mar 14;324(11):709-15. — View Citation

Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. — View Citation

Machiels JP, Duck L, Honhon B, Coster B, Coche JC, Scalliet P, Humblet Y, Aydin S, Kerger J, Remouchamps V, Canon JL, Van Maele P, Gilbeau L, Laurent S, Kirkove C, Octave-Prignot M, Baurain JF, Kartheuser A, Sempoux C. Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study. Ann Oncol. 2005 Dec;16(12):1898-905. Epub 2005 Oct 11. — View Citation

Ngan SY, Michael M, Mackay J, McKendrick J, Leong T, Lim Joon D, Zalcberg JR. A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer. Br J Cancer. 2004 Sep 13;91(6):1019-24. — View Citation

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

Rödel C, Grabenbauer GG, Papadopoulos T, Hohenberger W, Schmoll HJ, Sauer R. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol. 2003 Aug 15;21(16):3098-104. — View Citation

Rödel F, Hoffmann J, Grabenbauer GG, Papadopoulos T, Weiss C, Günther K, Schick C, Sauer R, Rödel C. High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection. Strahlenther Onkol. 2002 Aug;178(8):426-35. — View Citation

Ruzzo A, Graziano F, Loupakis F, Rulli E, Canestrari E, Santini D, Catalano V, Ficarelli R, Maltese P, Bisonni R, Masi G, Schiavon G, Giordani P, Giustini L, Falcone A, Tonini G, Silva R, Mattioli R, Floriani I, Magnani M. Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol. 2007 Apr 1;25(10):1247-54. Erratum in: J Clin Oncol. 2009 Jul 1;27(19):3262. — View Citation

Sawada N, Ishikawa T, Sekiguchi F, Tanaka Y, Ishitsuka H. X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res. 1999 Oct;5(10):2948-53. — View Citation

Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. — View Citation

Souglakos J, Androulakis N, Mavroudis D, Kourousis C, Kakolyris S, Vardakis N, Kalbakis K, Pallis A, Ardavanis A, Varveris C, Georgoulias V. Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1284-7. — View Citation

Stoehlmacher J, Park DJ, Zhang W, Yang D, Groshen S, Zahedy S, Lenz HJ. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer. 2004 Jul 19;91(2):344-54. — View Citation

Tveit KM, Guldvog I, Hagen S, Trondsen E, Harbitz T, Nygaard K, Nilsen JB, Wist E, Hannisdal E. Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group. Br J Surg. 1997 Aug;84(8):1130-5. — View Citation

Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. — View Citation

Van Cutsem E, Hoff PM, Harper P, Bukowski RM, Cunningham D, Dufour P, Graeven U, Lokich J, Madajewicz S, Maroun JA, Marshall JL, Mitchell EP, Perez-Manga G, Rougier P, Schmiegel W, Schoelmerich J, Sobrero A, Schilsky RL. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer. 2004 Mar 22;90(6):1190-7. — View Citation

Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year disease free survival rate		the day of surgery to the date of the event	Yes
Secondary	overall survival rate		the day of surgery to the date of death or last follow-up	Yes
Secondary	cumulative incidence of local recurrence		the day of surgery to the date of local recurrence	Yes
Secondary	cumulative incidence of distant metastasis		the day of surgery to the date of distant metastasis	Yes
Secondary	compliance		during adjuvant radiotherapy and chemotherapy	Yes
Secondary	safety		the day of randomization to the date of death or last follow-up	Yes