Study of Postoperative Concurrent Chemo-radiation With Capecitabine in Elderly Rectal Cancer Patients

Rectal Neoplasms Clinical Trial

Official title:

Phase 1 Study of Postoperative Capecitabine With Concurrent Radiation in Elderly With Stage II/III Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01268943
• Other study ID #: CH-GI-013
• Status: Completed
• Phase: Phase 1
• First received: December 28, 2010
• Last updated: March 17, 2015
• Start date: November 2010
• Est. completion date: January 2014

Study information

• Verified date: March 2015
• Source: Chinese Academy of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to seek the proper dose of capecitabine in post-operative concurrent chemotherapy for stage II/III elderly rectal cancer patients receiving radical surgery, and evaluate the toleration of this modality in such patients.

Description:

For those "younger" locally advanced (stage II/III) rectal cancer patients (usually means patients less than 70), it is suggested that after radical surgery, patients should receive concurrent chemo-radiation. Capecitabine is a widely used chemotherapy medicine under such condition. Based on experience, the investigators think this modality can also be tolerated by patients over 70, and will increase local control rate as which has been proved in younger ones. As the first step to test this hypothesis, we designed this phase I study to seek the proper dose of capecitabine, a widely used oral chemotherapy medicine, in postoperative concurrent chemo-radiation for stage II/III rectal cancer patients over 70, and to evaluate the safety of this modality in this group of patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 71 Years and older

Eligibility

Inclusion Criteria:

• rectal adenocarcinoma, pathological stage II/III(T3-4 or N+, UICC 2002), radical surgery received.

• interval between surgery and enrollment no less than two week and no more than 3 months.

• KPS status no less than 70; life expectancy no less than 6 months.

• without life-threatening complications, such as severe hypertension, coronary heart disease, cerebral vascular disease, uncontrolled diabetes, etc.

• without severe drug allergy history.

• hemoglobin >= 100g/L, white blood cell >= 3.5*10E9/L, neutrophil >= 1.5*10E9/L, platelet >= 100*10E9/L.

• Creatin <= 1.5* ULN(upper limit of normal), Total bilirubin <= 2.5 ULN, AST and AST <= 2.5* ULN, AKP <= 2.5*ULN

• do not receive chemotherapy before six months from enrollment.

• no previously pelvic irradiation history

• informed consent signed

Exclusion Criteria:

• other cancer history, except curable non-melanoma skin cancer or cervix in-situ carcinoma

• allergy history to thymidine phosphorylase

• previous pelvic irradiation history

• receiving adjuvant chemotherapy in six months before enrollment

• active infection existed

• severe complication, such as acute myocardial infarction in 6 months, uncontrolled diabetes ( Plasma glucose concentrations in any time of a day=11.1mmol/L), severe cardiac arrhythmia, etc.

• life expectancy less than 6 months

• estimated cannot finish treatment

• attend other clinical trials in four weeks before enrollment

• receive other anti-cancer treatment currently

• other conditions which regarded illegal by censors with full reasons. for example, some conditions may conflict from the protocol.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Neoplasms

Intervention

Drug:
• Capecitabine
oral pills, 1000mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation.
• Capecitabine
oral pills, 1200mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation.
• Capecitabine
oral pills, 1400mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation.
• Capecitabine
oral pills, 1500mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation.

Locations

Country	Name	City	State
China	radiation department, Cancer Hospital, CAMS	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

References & Publications (26)

Aapro MS, Köhne CH, Cohen HJ, Extermann M. Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist. 2005 Mar;10(3):198-204. Review. — View Citation

Abir F, Alva S, Longo WE. The management of rectal cancer in the elderly. Surg Oncol. 2004 Dec;13(4):223-34. Review. — View Citation

Bouvier AM, Launoy G, Lepage C, Faivre J. Trends in the management and survival of digestive tract cancers among patients aged over 80 years. Aliment Pharmacol Ther. 2005 Aug 1;22(3):233-41. — View Citation

Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet. 2001 Oct 20;358(9290):1291-304. — View Citation

Dobie SA, Warren JL, Matthews B, Schwartz D, Baldwin LM, Billingsley K. Survival benefits and trends in use of adjuvant therapy among elderly stage II and III rectal cancer patients in the general population. Cancer. 2008 Feb 15;112(4):789-99. doi: 10.1002/cncr.23244. — 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

Feliu J, Sereno M, Castro JD, Belda C, Casado E, González-Barón M. Chemotherapy for colorectal cancer in the elderly: Whom to treat and what to use. Cancer Treat Rev. 2009 May;35(3):246-54. doi: 10.1016/j.ctrv.2008.11.004. Epub 2009 Apr 2. Review. — View Citation

Fiorica F, Cartei F, Carau B, Berretta S, Spartà D, Tirelli U, Santangelo A, Maugeri D, Luca S, Leotta C, Sorace R, Berretta M. Adjuvant radiotherapy on older and oldest elderly rectal cancer patients. Arch Gerontol Geriatr. 2009 Jul-Aug;49(1):54-9. doi: 10.1016/j.archger.2008.05.001. Epub 2008 Jun 24. — View Citation

Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. — View Citation

Folprecht G, Cunningham D, Ross P, Glimelius B, Di Costanzo F, Wils J, Scheithauer W, Rougier P, Aranda E, Hecker H, Köhne CH. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004 Sep;15(9):1330-8. — View Citation

Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. Erratum in: J Clin Oncol. 2008 Jun 10;26(17):2925-6. — View Citation

Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. — 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

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

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

Papamichael D, Audisio R, Horiot JC, Glimelius B, Sastre J, Mitry E, Van Cutsem E, Gosney M, Köhne CH, Aapro M; SIOG. Treatment of the elderly colorectal cancer patient: SIOG expert recommendations. Ann Oncol. 2009 Jan;20(1):5-16. doi: 10.1093/annonc/mdn532. Epub 2008 Oct 15. Review. — View Citation

Pasetto LM, Monfardini S. The role of capecitabine in the treatment of colorectal cancer in the elderly. Anticancer Res. 2006 May-Jun;26(3B):2381-6. Review. — View Citation

Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002 Mar 1;20(5):1192-202. — 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

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

Surgery for colorectal cancer in elderly patients: a systematic review. Colorectal Cancer Collaborative Group. Lancet. 2000 Sep 16;356(9234):968-74. Review. — 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

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

Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. — 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

Zhu AX, Willett CG. Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer. Semin Radiat Oncol. 2003 Oct;13(4):454-68. Review. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Related Toxicity	dose related toxicity is defined as follows:1. WBC damage >= grade 3; granular cell decrease >= grade 3; hemoglobin >= grade 2; platelet >= grade 2;SGPT/SGOT elevation >= grade 2; ALP >= grade 2; GGT >= grade 2; Tbil >= grade 2;renal function damage: BUN/Cr elevation >= grade 2;Non-gradular cell decreased fever >= grade 2;nausea/vomiting >= grade 2; fatigue >= grade 3; weight loss >= grade 3;gastritis >= grade 3; dairrea >= grade 3; abdominal pain >= grade 3; pancreatitis >= grade 2; upper gastrointestinal bleeding >= grade 2;other toxic reaction >= grade 3;KPS < 50 during the treatment	up to 9 weeks	Yes