Prospective Comparisons of Clinical Trial and Real-world Outcomes in Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Prospective Comparisons of Survival Outcomes, Safety Profile, and Probability of Returning to Society Between Three Randomized Controlled Trials and Real-world Evidence in Nasopharyngeal Carcinoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04108338
• Other study ID #: 2019-FXY-239
• Status: Completed
• Start date: June 1, 2019
• Est. completion date: August 1, 2019

Study information

• Verified date: September 2019
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Study results from randomized controlled trials (RCTs) usually have been found not adequately inform practice. A RCT is optimized to determine efficacy, while real-world study is conducted in a routine care setting aimed to determine effectiveness. Thus, it is necessary to evaluate the pragmatism of clinical trials for a better understanding of the external generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world studies still lack well elucidation. By capitalizing on a nasopharyngeal carcinoma (NPC)-specific big-data, real-world database and individual patient data extracted from three landmark RCTs, investigators conducted the direct comparison of NPC cohorts receiving same treatment strategy in clinical trial versus real-world settings, and examined the comparative pragmatic features and their influences on survival outcomes, safety profile, and the probability of returning to society.

Description:

Study results from randomized controlled trials (RCTs) usually have been found not adequately inform practice. A RCT is optimized to determine efficacy. Such trials were performed with relatively small samples at sites with experienced investigators and highly selected participants, they could be overestimating benefits and underestimating harm. Real-world study is conducted in a routine care setting aimed to determine effectiveness. Thus, it is necessary to evaluate the pragmatism of clinical trials for a better understanding of the external generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world studies still lack well elucidation. Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with the highest incidences in endemic regions such as Southern China, where over 60,600 new cases were diagnosed in 2015 representing 40% of all cases worldwide. Studies conducted in China are critical in optimizing clinical decision-making of NPC. In the past two decades, the recommendation level of induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) has been improved evidently from Category 3 to 2A, and CCRT alone has long been a stable (Category 2B) and classic treatment option of NPC and therefore becomes the most commonly used control group in comparative studies. By capitalizing on a NPC-specific big-data, real-world database via a cancer registry in Southern China and individual patient data extracted from the three landmark RCTs, investigators conducted the direct comparison on IC+CCRT cohort or CCRT cohort of clinical trial versus real-world settings, and examined the comparative pragmatic features and their influences on survival outcomes, safety profile, and the probability of returning to society, with the aim to provide new insight into the optimization of trial design and the translation of study evidences into tangible benefits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5448
• Est. completion date: August 1, 2019
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 79 Years

Eligibility

Inclusion Criteria:

1. Patients treated in our center from April 2009 to December 2016;

2. All patients were pathologically diagnosed, non-metastatic nasopharyngeal carcinoma;

3. Only included cases staged as T3-4N1 & T1-4N2-3 according to the 6th or 7th edition American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) system;

4. For trial patients, treatment strategies only limited to concurrent chemoradiotherapy, induction chemotherapy combined with concurrent chemoradiotherapy, or concurrent chemoradiotherapy combined with adjuvant chemotherapy;

5. For patients from real-world database, patients are permitted to receive additional targeted therapy to standard chemoradiotherapy, as far as it met clinical needs and was approved by physicians.

6. The patient's basic information, prognosis related data, and follow-up data are complete.

Exclusion Criteria:

1. The clinical stage of T3-4N0 was excluded;

2. Cases from large real-world databases need to exclude patients who participate in clinical trials;

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma

Intervention

Other:
• Trial setting
Study results from clinical trials usually have been found not work efficiently in clinical practice. This outcome disparity may be caused by different pragmatic features of medical environment, also known as study setting such as trial setting and real-world setting, in which biases inherent to clinical trial design restrict its applicability even though all confounding factors are avoided.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (5)

Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer. 2014 Feb 4;110(3):551-5. doi: 10.1038/bjc.2013.725. Epub 2014 Jan 14. — View Citation

Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7. — View Citation

Prince RM, Atenafu EG, Krzyzanowska MK. Hospitalizations During Systemic Therapy for Metastatic Lung Cancer: A Systematic Review of Real World vs Clinical Trial Outcomes. JAMA Oncol. 2015 Dec;1(9):1333-9. doi: 10.1001/jamaoncol.2015.3440. Review. — View Citation

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. — View Citation

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive.	5-year
Primary	Failure-free survival (FFS)	Failure-free survival is measured from day of diagnosis to locoregional failure, distant failure, or death from any cause, whichever occurred first.	5-year
Primary	Locoregional failure-free survival (LRFFS)	Locoregional failure-free survival is measured from day of diagnosis to first locoregional failure.	5-year
Primary	Distant failure-free survival (DFFS)	Distant failure-free survival is measured from day of diagnosis to distant failure.	5-year
Primary	Probability of studying/work stoppage caused by disease and treatment	Probability of learning (students who are in college/university/school before illness) or work (staff who are working before illness) stoppage due to illness and treatment.	5-year
Primary	Probability of returning to studying/work after suspending	Probability of returning to learning (students who are in college/university/school before illness) or work (staff who are working before illness) after suspending due to illness and treatment.	5-year
Secondary	Incidence of radioactive brain injury	Incidence of radioactive brain injury according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of hearing loss	Incidence of hearing loss according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of blind	Incidence of blind according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of decreased taste	Incidence of decreased taste according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of second cancer	Incidence of second cancer according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of dysphagia	Incidence of dysphagia according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of malnutrition	Incidence of malnutrition according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Secondary	Incidence of hypothyroidism	Incidence of hypothyroidism according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year