Clinical trial NCT04108338: Prospective Comparisons of Clinical Trial and Real-world Outcomes in Nasopharyngeal Carcinoma
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Nasopharyngeal Carcinoma
Keywords: Clinical trial
Real-world study
Nasopharyngeal carcinoma
Pragmatism
Survival
Return to society
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-09-30
Enrollment: 5448
Sex: ALL
Minimum age (years): 8
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Overall survival
timeFrame: 5-year
measure: Failure-free survival (FFS)
timeFrame: 5-year
measure: Locoregional failure-free survival (LRFFS)
timeFrame: 5-year
measure: Distant failure-free survival (DFFS)
timeFrame: 5-year
measure: Probability of studying/work stoppage caused by disease and treatment
timeFrame: 5-year
measure: Probability of returning to studying/work after suspending
timeFrame: 5-year
Secondary outcomes:
measure: Incidence of radioactive brain injury
timeFrame: 5-year
measure: Incidence of hearing loss
timeFrame: 5-year
measure: Incidence of blind
timeFrame: 5-year
measure: Incidence of decreased taste
timeFrame: 5-year
measure: Incidence of second cancer
timeFrame: 5-year
measure: Incidence of dysphagia
timeFrame: 5-year
measure: Incidence of malnutrition
timeFrame: 5-year
measure: Incidence of hypothyroidism
timeFrame: 5-year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Jun Ma, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
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