Single-agent Capecitabine as Adjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma (CAN)

• ClinicalTrials.gov Identifier: NCT02958111
• Recruitment Status: Unknown
• First Posted: November 8, 2016
• Last Update Posted: June 12, 2019
• Sponsor: Sun Yat-sen University
• Collaborators: Tongji Hospital; Wuhan Union Hospital, China; Peking University; Air Force Military Medical University, China; Second Affiliated Hospital of Soochow University; West China Hospital; The First Affiliated Hospital of Guangdong Pharmaceutical University; First People's Hospital of Foshan; Fifth Affiliated Hospital, Sun Yat-Sen University; Cancer Hospital of Guizhou Province; Xiangya Hospital of Central South University; First Affiliated Hospital of Zhejiang University; Jilin Provincial Tumor Hospital; Henan Cancer Hospital; Hunan Cancer Hospital; The First Affiliated Hospital of Xiamen University; Cancer Hospital of Guangxi Medical University
• Information provided by (Responsible Party): Jun Ma, MD, Sun Yat-sen University

Tracking Information

• First Submitted Date: October 26, 2016
• First Posted Date: November 8, 2016
• Last Update Posted Date: June 12, 2019
• Study Start Date: January 2017
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 4, 2016): Progression-free survival [ Time Frame: 3 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 19, 2018)

• Overall survival [ Time Frame: 3 years ]
• Distant failure-free survival [ Time Frame: 3 years ]
• Locoregional failure-free survival [ Time Frame: 3 years ]
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1 year ]
• Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30 [ Time Frame: 1 year ]

Original Secondary Outcome Measures (submitted: November 4, 2016)

• Overall survival [ Time Frame: 5 years ]
• Distant failure-free survival [ Time Frame: 3 years ]
• Locoregional failure-free survival [ Time Frame: 3 years ]
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1 year ]
• Quality of life (QOL) as assessed by EORTC quality of life questionnaire(QLQ)-C30 [ Time Frame: 1 year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Single-agent Capecitabine as Adjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
• Official Title: Single-agent Capecitabine as Adjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase 3, Multicentre, Randomised Controlled Trial (CAN)
• Brief Summary: This is an randomized, controlled, multicenter phase 3 clinical trial. The purpose of this study is to evaluate the efficacy and safety of single-agent capecitabine as adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC).
• Detailed Description: In this study, NPC patients (stage III-IV A, except T3-4 N0 and T3 N1) who finished the curative radiotherapy will be randomized to the observation group and capecitabine group (650 mg/m2 bid, p.o.，d1-21，q3wks; continued until disease progression, unacceptable toxicity, or over 1 year). The primary endpoint is progression-free survival (PFS). Secondary end points include overall survival (OS), distant failure-free survival (D-FFS), locoregional failure-free survival (LR-FFS), toxic effects, and quality of life (QOL). All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Nasopharyngeal Carcinoma

Intervention

Drug: Capecitabine

Patients will receive capecitabine (650 mg/m2 bid, p.o.，d1-21，q3wks; continued until disease progression, unacceptable toxicity, or over 1 year).

Study Arms

• Experimental: Adjuvant capecitabine
  Adjuvant chemotherapy with single-agent capecitabine
  Intervention: Drug: Capecitabine
• No Intervention: Observation
  Clinical follow-up and surveillance only

Publications *

• Liu YC, Wang WY, Twu CW, Jiang RS, Liang KL, Wu CT, Lin PJ, Huang JW, Hsieh HY, Lin JC. Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients. Oral Oncol. 2017 Jan;64:15-21. doi: 10.1016/j.oraloncology.2016.11.008. Epub 2016 Nov 30.
• Twu CW, Wang WY, Chen CC, Liang KL, Jiang RS, Wu CT, Shih YT, Lin PJ, Liu YC, Lin JC. Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid. Int J Radiat Oncol Biol Phys. 2014 May 1;89(1):21-9. doi: 10.1016/j.ijrobp.2014.01.052.
• Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.
• Ribassin-Majed L, Marguet S, Lee AWM, Ng WT, Ma J, Chan ATC, Huang PY, Zhu G, Chua DTT, Chen Y, Mai HQ, Kwong DLW, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Bourhis J, Pignon JP, Blanchard P. What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol. 2017 Feb 10;35(5):498-505. doi: 10.1200/JCO.2016.67.4119. Epub 2016 Dec 5.
• Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. doi: 10.1200/JCO.2010.33.9101. Epub 2011 Oct 24.
• Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM, Tol J, Braun HJ, Nieboer P, van der Hoeven JJ, Haasjes JG, Jansen RL, Wals J, Cats A, Derleyn VA, Honkoop AH, Mol L, Punt CJ, Koopman M. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015 May 9;385(9980):1843-52. doi: 10.1016/S0140-6736(14)62004-3. Epub 2015 Apr 7.
• Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. doi: 10.1016/S1470-2045(16)30410-7. Epub 2016 Sep 27.
• Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23. Erratum In: Lancet. 2016 Oct 15;388(10054):1882.
• Hui EP, Ma BB, Leung SF, King AD, Mo F, Kam MK, Yu BK, Chiu SK, Kwan WH, Ho R, Chan I, Ahuja AT, Zee BC, Chan AT. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009 Jan 10;27(2):242-9. doi: 10.1200/JCO.2008.18.1545. Epub 2008 Dec 8.
• Chen YP, Liu X, Zhou Q, Yang KY, Jin F, Zhu XD, Shi M, Hu GQ, Hu WH, Sun Y, Wu HF, Wu H, Lin Q, Wang H, Tian Y, Zhang N, Wang XC, Shen LF, Liu ZZ, Huang J, Luo XL, Li L, Zang J, Mei Q, Zheng BM, Yue D, Xu J, Wu SG, Shi YX, Mao YP, Chen L, Li WF, Zhou GQ, Sun R, Guo R, Zhang Y, Xu C, Lv JW, Guo Y, Feng HX, Tang LL, Xie FY, Sun Y, Ma J. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021 Jul 24;398(10297):303-313. doi: 10.1016/S0140-6736(21)01123-5. Epub 2021 Jun 7.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: June 11, 2019): 406
• Original Estimated Enrollment (submitted: November 4, 2016): 402
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age 18-65
2. Performance status of Eastern Cooperative Oncology Group (ECOG) grade 0 or 1
3. Tumor staged as American Joint Committee on Cance (AJCC) III-IV A (except T3-4 N0, T3 N1), with newly histologically confirmed non-keratinizing NPC
4. Within 12-16weeks after completion of the recommended curative radiotherapy treatment
5. No clinical evidence of persistent loco-regional disease or distant metastases after radiotherapy
6. Complete the recommended concurrent chemotherapy ± induction chemotherapy
7. Adequate hematologic (neutrophil count > 1.5×10^9/L, hemoglobin > 90g/L and platelet count > 100×10^9/L), hepatic (alanine aminotransferase, aspartate aminotransferase ≤ 1.5×ULN, bilirubin ≤ 1.5×ULN, alkaline phosphatase < 2.5×ULN) and renal function (creatinine clearance > 50 ml/min)
8. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. Patients who could not tolerate or allergic to capecitabine.
2. Illness that would interfere with oral medication, including dysphagia, chronic diarrhea, or ileus
3. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer.
4. Pregnancy or lactation (consider pregnancy test in women of child-bearing age and emphasize effective contraception during the treatment period).
5. Patients who received surgery treatment, biotherapy or immunotherapy during or before radiotherapy.
6. Patients who are receiving or highly likely to receive other chemotherapy treatment, biotherapy or immunotherapy.
7. History of previous radiotherapy before the curative radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume).
8. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes before the curative radiotherapy
9. Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose > 1.5×ULN), and emotional disturbance.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02958111
• Other Study ID Numbers: 2016-FXY-075
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Jun Ma, MD, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

Collaborators

• Tongji Hospital
• Wuhan Union Hospital, China
• Peking University
• Air Force Military Medical University, China
• Second Affiliated Hospital of Soochow University
• West China Hospital
• The First Affiliated Hospital of Guangdong Pharmaceutical University
• First People's Hospital of Foshan
• Fifth Affiliated Hospital, Sun Yat-Sen University
• Cancer Hospital of Guizhou Province
• Xiangya Hospital of Central South University
• First Affiliated Hospital of Zhejiang University
• Jilin Provincial Tumor Hospital
• Henan Cancer Hospital
• Hunan Cancer Hospital
• The First Affiliated Hospital of Xiamen University
• Cancer Hospital of Guangxi Medical University

• Investigators: Not Provided
• PRS Account: Sun Yat-sen University
• Verification Date: June 2019