This document discusses multicentric clinical trials. It begins by defining clinical trials and introducing that a multicenter trial is conducted across multiple medical centers. Key points are that multicenter trials require standardization of procedures, uniformity, high data quality, and collaboration across sites. The document distinguishes between multi-site and multicentric studies, noting that in multicentric studies investigators at sites are co-investigators in planning and responsible for results, while in multi-site studies sites merely carry out tasks. Coordination in multicenter studies involves centralized activities like protocol development and data management to standardize procedures. Advantages include larger sample sizes and evaluating efficacy across populations. The document concludes by summarizing a phase II multicenter trial of sunit

1. MULTICENTRIC TRIALS
PRESENTED BY:
SwATI SARIN
JAgMohAN
hARDIPENDER

2. CLINICAL TRIAL
“Study of drug, biologic or device in human subjects with the intent
to discover potential beneficial effects and/or determine its safety
and efficacy.”
OR
“Clinical trials are research studies in which people help doctors find
ways to improve health and cancer care. Each study tries to
answer scientific questions and to find better ways to prevent,
diagnose, or treat cancer.”

3. INTRoDUCTIoN
A multicenter research trial is a clinical trial
conducted at more than one medical center or clinic.

4. KEY PoINTS IN
MUTICENTRIC STUDIES
 needs to assure standardization
 uniformity of procedures
 high data quality
 collaboration across sites

5. DISTINCTIoN BETwEEN MULTI-SITE
STUDIES AND
MULTICENTER STUDIES
In both types of studies, multiple institutions perform the same
procedures as others.
MULTICENTRE STUDIES
The investigators at the sites are
involved as co-investigators in the
planning of the study protocol and
procedures.
They scientifically responsible for
the study results, and participate in
manuscripts and other
dissemination activities.
MULTI SITE STUDIES
 The investigators at the sites do not
participate as co-investigators of the study
They are merely carrying out the study
(e.g. recruiting subjects, treating subjects,
and/or following subjects) and thus can be
viewed as contractors

6. CooRDINATIoN IN MULTI SITE
STUDIES
 In a multi-site study, activities of protocol development ,development of
study materials, training, communication, laboratory determinations, data
processing and management, report generation, statistical analysis, and
manuscript development are often centralized because of the need to
standardize them across all sites, which often also has the further benefit of
resulting in a gain of cost efficiency.
 The central group ‘controls’ the data and hence the study; and must take
steps to assure other participating institutions that it is managing it
adequately.
 This assurance is provided by developing adequate systems for staff training
and quality assurance, collecting, entering, managing and analyzing the data.
These activities are done by the statistical coordinating center

10. AdvAntAges
 larger number of participants,
 Different geographic locations,
 The possibility of inclusion of a wider range of population groups,
 The ability to compare results among centers,
All of which increase the generalizability of the study
 In many cases, efficacy will vary significantly between population
groups with different genetic, environmental, and ethnic or cultural
backgrounds ("demographic" factors); normally only geographically
dispersed trials can properly evaluate this.

11. enrollment of subjects
 Enrollment should be competitive.
 If the subject recruitment rate is lower than expected at one centre and
higher than expected at another, planned allocation numbers should be
transferred from the centre with low subject recruitment to a centre with
high recruitment where subject inclusion is expected to be completed
earlier than planned. This will be done to help ensure that subject
enrollment is completed as planned.

12. set up costs
The low set up costs should be negotiated in order to enable to sign
agreements with larger number of sites

13. recruitment rAte
 Expected subject recruitment rate should be evaluated.
 Subject enrollment ends when the planned number of subjects is
reached.
 The recruitment rates estimate should be based on retrospective
data provided by the investigator(s) from previous studies, i.e., on
the number of subjects who would have satisfied the proposed
inclusion/exclusion criteria in the past.

14. contd…
 The investigator(s) should make every effort to ensure that the planned
accrual rate is maintained
 CRF’s are completed promptly and completely, and that data quality is
maintained at all times.
 The investigator(s) should discuss with the monitor any anticipated problems
with recruitment or delays in study completion.
 Number of sites for the study depends on estimated recruitment rates.

15. multicenter, phAse ii triAl of
sunitinib in previously treAted,
AdvAnced non–smAll-cell lung
cAncer
Journal of Clinical Oncology, Vol 26, No 4 (February 1), 2008:
pp. 650-656

16. introduction
Lung cancer remains the leading cause of cancer-related mortality
worldwide, accounting for 1.18 million deaths per year.

17. Contd…
 Non–small-cell lung cancer (NSCLC)
 Vascular endothelial growth factor (VEGF)
 Platelet-derived growth factor (PDGF)
 Growth factors that play an important role in tumor growth.

18. PurPose
Aberrant vascular endothelial growth factor (VEGF) and platelet-derived
growth factor (PDGF) signaling have been shown to play a role in non–
small-cell lung cancer (NSCLC) pathogenesis and are associated with
decreased survival.

19. PurPose Contd..
Evaluate the clinical activity and tolerability of sunitinib malate
(SU11248), an oral, multi targeted tyrosine kinase inhibitor that blocks
the activity of receptors for VEGF and PDGF, as well as related
tyrosine kinases in patients with previously treated, advanced NSCLC.

20. Patients
Male and female patients 18 years of age or older had histologically
proven stage IIIB or IV NSCLC which had progressed during or
after treatment with at least one platinum-based combination
chemotherapy regimen

21. study design and
treatment
 Phase II
 Open-label
 Multicenter study
 Patients received sunitinib (50 mg/d) in 6-week cycles, comprising
once-daily treatment for 4 consecutive weeks, followed by 2 weeks of
no treatment
 Treatment was otherwise administered for up to 54 weeks until
disease progression or withdrawal of consent occurred

22. assessment
 The primary end point was objective response rate (ORR)
 Secondary end points included progression-free survival, overall
survival, and safety

23. end Points
 Endpoint is the overall outcome that the protocol is designed to evaluate.
 PRIMARY ENDPOINTS
 These are the principal outcomes that the investigator is looking for.
 Cure
 Sometimes difficult to reach
 SECONDARY ENDPOINTS
 Evaluated when a significant number of trial subjects fail to reach the primary
end point , secondary end points help analyze the trial data

24. Contd..
 The primary end point of this study was the overall confirmed
objective response rate (ORR),
defined as the percentage of patients with confirmed complete
responses (CRs) or partial responses (PRs) based on radiologic tumor
assessments (computed tomography, magnetic resonance imaging,
and bone scans as appropriate)
 Imaging scans included the chest, abdomen, and pelvis and were
collected at the end of dosing in cycles 1 to 4, 6, and 8, and at study
termination.

25. Contd…
 Other evaluations included medical history, physical examination
(including height, weight, and vital sign measurements), laboratory
tests (urinalysis, hematology, coagulation, and blood chemistry),
cardiac function (12-lead ECGs), and adverse events (AEs)
 Progression-free survival (PFS), duration of response (DR), overall
survival (OS), and the 1-year survival rate were evaluated as secondary
end points of the study.

26. Results
Of the 63 patients treated with sunitinib
 Seven patients had confirmed partial responses, yielding an ORR
of 11.1%
 An additional 18 patients (28.6%) experienced stable disease of at
least 8 weeks in duration.
 Therapy was generally well tolerated.

27. ConClusion
Sunitinib has promising single-agent activity in patients with recurrent
NSCLC, with an ORR similar to that of currently approved agents and
an acceptable safety profile.

28. RefeRenCes
 Journal of Clinical Oncology, Vol 26, No 4 (February 1), 2008: pp. 650-
656 © 2008 American Society of Clinical Oncology.
 Shrikant I. Bangdiwala, PhD,(1) Cristiane S. de Paula, MS,(2) Laurie
S. Ramiro, PhD,(3) Sergio R. Muñoz, PhD.(4); Coordination of
international multicenter studies
 Governance and administrative structure
 en.wikipedia.org/wiki/Multicenter_trial
 www.nih.gov/news/health/sep2008/nci-1

29. Questions ??

30. thank You!!!