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

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.

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.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Other: Trial setting

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 5448

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 79 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with locoregionally advanced nasopharyngeal carcinoma (T3-4N1 and T1-4N2-3). There are two parts of the constitution of study population.

Part 1. 1,468 subjects from three phase 3 randomized controlled trials ((NCT00677118, NCT01245959, and NCT01872962) that were conducted by our research team and had been published.

Part 2. 3,980 subjects from the NPC-specific big-data, real-world database via a cancer registry in Southern China.

Description

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;

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CCRT-randomized clinical trial; Trial patients receiving CCRT	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.; Other Names: Explanatory medical environment; Non-pragmatic features
CCRT-real-world database; Patients receiving CCRT from real-world database
IC+CCRT-randomized clinical trial; Trial patients receiving IC+CCRT	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.; Other Names: Explanatory medical environment; Non-pragmatic features
IC+CCRT-real-world database; Patients receiving IC+CCRT from real-world database

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive.	5-year
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
Locoregional failure-free survival (LRFFS)	Locoregional failure-free survival is measured from day of diagnosis to first locoregional failure.	5-year
Distant failure-free survival (DFFS)	Distant failure-free survival is measured from day of diagnosis to distant failure.	5-year
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of radioactive brain injury	Incidence of radioactive brain injury according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of hearing loss	Incidence of hearing loss according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of blind	Incidence of blind according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of decreased taste	Incidence of decreased taste according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of second cancer	Incidence of second cancer according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of dysphagia	Incidence of dysphagia according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of malnutrition	Incidence of malnutrition according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year
Incidence of hypothyroidism	Incidence of hypothyroidism according to the Common Terminology Criteria for Adverse Events (version 4.0).	5-year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jun Ma, Professor, Sun Yat-sen University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 26, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Survival; Clinical trial; Nasopharyngeal carcinoma; Real-world study; Pragmatism; Return to society
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: 2019-FXY-239

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No