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.”
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
7.
8.
9.
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.
