Download Clinical Trials

Modified Megestrol
The Clinical Trials
by :
Carolina R. Akib
[email protected]
Our product
It is
”Modified Megestrol”,
estrogen agonist, for treat HCC.
After aprroval IND from Thai FDA
we will start our CLINICAL TRIALS.
Objectives
• RATIONALE: Estrogen can stimulate the growth
of cancer cells. Hormone therapy using modified
megestrol may fight liver cancer by blocking the
uptake of estrogen. It is not yet known if
modified megestrol is an effective treatment for
liver cancer.
• PURPOSE : Trial to determine the effectiveness
of modified megestrol in treating patients who
have liver cancer that cannot be removed by
surgery.
Trial Protocol
- Protocol is written document by the
sponsor of the study and explains :
What the trial will do,
How it will be conduct,
Where it will be conduct,
Who may participate,
How and when the participate will be
evaluated.
Participant / Patients
• Informed written consent
& explanation about
process, risk & benefits,
insurance
ELIGIBILITY
(INCLUSION &
EXCLUSION CRITERIA)
Disease Characterize :
Diagnosis of HCC:
Measurable, Estrogen
receptor (+), Not amenable
to surgery, No metastases,
No previous or simultaneous
secondary malignant
disease
Participant / Patients, cont….
Patient Characteristic
Age
: Over 18
Gender : Both
Performance status : Karnofsky scale ≥ 70
Life expectancy : At least 12 weeks
Function of organs :
Hepatic : SGOT, bilirubin, albumin
Renal : Creatinin
Other
: Not pregnant or nursing
Fertile patients
No physical illness
No other malignancy
Participant / Patients, cont….
Prior Concurrent Therapy :
Biologic therapy : Not specified
Chemotherapy
: No chemoembolization,
chemotherapy, antihormonal therapy
Endocrine therapy : Not specified
Radiotherapy : Not specified
Surgery
: No prior surgery for HCC
Other : No prior percutaneous injection-HCC
Trial Sites
Multicenter –
University hospitals in Bangkok
Mahidol University Hospital
King Chulalongkorn University Hospital
Thammasat University Hospital
National Cancer Center Hospital
Phase I
Objectives:
 To define tolerable dose (MTD) of Modified Megestrol.
 Describe common side effects
 Describe pharmacologics in humans
Number of participant (Study size) :
15-30 patients (3-6 cohort w/ 3-6 patients each cohort)
Medications & Dosages:
Starting dose: 0.1 x LD10 from preclinical trial, increase (dose
escalation)  MTD.
Length of the study: 3-6 months
Evaluation time : baseline & every 2 months.
Variable : General Scale of Grading Toxicity from WHO.
Phase II
Objectives :
 Response rate (the ability of the Modified Megestrol to
produce tumor shrinkage), survival, quality of life.
 Possibly pharmacodynamics relationship
Number of participant (Study size) :
< 100 patients
Medications & Dosages:
Starting dose range MTD  fixed dose
Length of the study: 3-6 months
Evaluation time : baseline & every 2 month
Variable : Tumor response & Survival.
Phase III
A randomized, double-blind, multicenter
study. Patients are randomized to 1 of 2
treatment arms.
Objectives:
Compare the overall survival of patients
with inoperable HCC treated with Modified
Megestrol vs Original Megestrol.
Compare the quality of life of patients
treated with these drug.
Phase III, cont …
Number of participant (Study size) :
100-thousands patients
• Arm I: Patients receive fixed dose of
Modified Megestrol for 1 year.
Arm II: Patients receive oral Original
Megestrol for 1 year.
• Quality of life is assessed at baseline and
then monthly for 1 year.
Schematic of the Phase III
Source population of patients with HCC
Recruit &
Register
Randomized CT study sample
Randomize
Patients
Modified M (n=200)
Original M (n=100)
Treat, monitor, evaluate, and compare outcomes
Phase IV
Start after FDA approves NDA of Modified
Megestrol.
Objectives:
late / uncommon effects of Modified
Megestrol
Medications & Dosages:
Fixed dose of Modified Megestrol
Sample size : 2000-3000
Length of the study : 10 years
Data Processing
Data Handling
All calculations will perform with recent
statistical package.
Variable :Tumour response: histologic,
size, function of organs,
Quality of life : changes in appetite, BW,
feeling of well-being, survival.
Record Keeping,
Independent data Monitoring Committee
Summary
Phase III
Phase IV
Phase I
Phase II
Monitor
variable
Size
Dosage
Function of
organs
20-40
0.1LD10
MTD
Tumor resp, Tumor resp,
Quality of L Quality of L
25-50
150-300
Other side
effects
2000-3000
80% MTD
 fixed
dose
Fixed dose
Length
3-6 month
3-6 month
I: Fixed dose
of MM
II: OM
1 year
Endpoints
MTD
(Rx
threshold)
efficacy &
fixed dose
(safety &
efficacy)
comparing
treatment
(randomized
CT)
late/
uncommon
effects
10 years