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

Purpose

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.

Condition	Intervention	Phase
Rectal Neoplasms	Drug: Capecitabine	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase 1 Study of Postoperative Capecitabine With Concurrent Radiation in Elderly With Stage II/III Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Capecitabine

U.S. FDA Resources

Further study details as provided by Chinese Academy of Medical Sciences:

Primary Outcome Measures:

dose related toxicity [ Time Frame: up to 9 weeks ] [ Designated as safety issue: Yes ]
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

Estimated Enrollment:	30
Study Start Date:	November 2010
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1000mg capecitabine 1000mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1000mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 1
Experimental: 1200mg capecitabine 1200mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1200mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 2
Experimental: 1400mg capecitabine 1400mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1400mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 3
Experimental: 1500mg capecitabine 1500mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1500mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 4
Experimental: 1600mg capecitabine 1600mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1600mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 5
Experimental: 1700mg capecitabine 1700mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1700mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 6
Experimental: 1800mg capecitabine 1800mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1800mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 7
Experimental: 1900mg capecitabine 1900mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1900mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 8
Experimental: 2000mg capecitabine 2000mg/m2/d d1-14, d22-35 combined with concurrent radiotherapy will be given to enrolled patients.	Drug: Capecitabine oral pills, 1900mg/m2/d, split in two times, d1-14, d22-35 combined with concurrent pelvic radiation. Other Name: stair 9

Detailed 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.

Eligibility

Ages Eligible for Study:	71 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268943

Contacts

Contact: Yu Tang, Ph.D.	8601087788504	tangyu.pumc@gmail.com
Contact: Jing Jin, Ph.D.	8601087788504

Locations

China, Beijing
radiation department, Cancer Hospital, CAMS	Recruiting
Beijing, Beijing, China, 100021
Contact: Yu Tang, Ph.D. 08601087788504 tangyu.pumc@gmail.com
Contact: Jing Jin, Ph.D. 08601087788122 tangyu.pumc@gmail.com
Principal Investigator: Yexiong Li, Ph.D.
Principal Investigator: Jing Jin, Ph.D.

Sponsors and Collaborators

Chinese Academy of Medical Sciences

Investigators

Principal Investigator:	Jing Jin, Ph.D.	radiation department, cancer hospital, CAMS
Principal Investigator:	Yexiong Li, Ph.D.	Radiation Department, Cancer Hospital, CAMS

More Information

Publications:

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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.

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.

[No authors listed] 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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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. Epub 2008 Oct 15. Review.

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. Epub 2008 Jun 24.

[No authors listed] Surgery for colorectal cancer in elderly patients: a systematic review. Colorectal Cancer Collaborative Group. Lancet. 2000 Sep 16;356(9234):968-74. Review.

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.

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.

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.

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. Epub 2009 Apr 2. Review.

Responsible Party:	Jing Jin, M.D., vice chair of radiation department, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier:	NCT01268943 History of Changes
Other Study ID Numbers:	CH-GI-013
Study First Received:	December 28, 2010
Last Updated:	April 20, 2012
Health Authority:	China: Food and Drug Administration

Keywords provided by Chinese Academy of Medical Sciences:

rectal neoplasms
aged
radiotherapy

drug therapy
dose-escalation
capecitabine

Additional relevant MeSH terms:

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

Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013