| CTRI Number |
CTRI/2009/091/000193 [Registered on: 12/06/2009] |
| Last Modified On: |
30/11/2012 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer |
Scientific Title of Study
Modification(s)
|
A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer
ENTHUSEM1C |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| D4320C00033 |
Protocol Number |
| NCT00617669 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Denzil Benjamin |
| Designation |
|
| Affiliation |
Senior Director |
| Address |
ICON Clinical Research , No.56/4, Sharadha Towers, Unit II 2 nd floor Nandidurg Road
Bangalore
KARNATAKA
560046
India |
| Phone |
8040304001 |
| Fax |
8041535656 |
| Email |
denzil.benjamin@iconplc.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Muppavarapu Venkataraghuram |
| Designation |
|
| Affiliation |
Assistant Director Mediacl Affairs |
| Address |
ICON Clinical Research , No.56/4, Sharadha Towers, Unit II 2 nd floor Nandidurg Road
Bangalore
KARNATAKA
560046
India |
| Phone |
91-40-43902988 |
| Fax |
91-80-41535656 |
| Email |
v.muppavarapu@iconplc.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Denzil Benjamin |
| Designation |
|
| Affiliation |
|
| Address |
ICON Clinical Research , No.56/4, Sharadha Towers, Unit II 2 nd floor Nandidurg Road
Bangalore
KARNATAKA
560046
India |
| Phone |
91-80-40394001 |
| Fax |
91-80-41535656 |
| Email |
denzil.benjamin@iconplc.com |
|
Source of Monetary or Material Support
Modification(s)
|
| AstraZeneca AB, 151 85 Södertälje, Sweden |
|
Primary Sponsor
Modification(s)
|
| Name |
AstraZeneca AB |
| Address |
AstraZeneca AB 151 85 Södertälje Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
|
Countries of Recruitment
Modification(s)
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 13 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr.Chanchal Goswami |
B P Poddar Hospital |
71/1, Humayun Kabir Sarani,,New Alipore, Block G,-700053
Kolkata
WEST BENGAL |
91 9830055035
91 33 24577009
chanchalg@sify.com |
| Dr. Shekhar Patil |
Bangalore Institute of Oncology |
HCG Towers, 1st Floor Triesta Sciences,, # 8 P.Kalinga Rao Road, Sampangiramnagar-560027
Bangalore
KARNATAKA |
919341245961
918022484519
sp_associates6@rediffmail.com |
| Dr. Raju Chacko |
Christian Medical College & Hospital |
Dept. of Oncology, CMC & H,,-632004
Vellore
TAMIL NADU |
91 9443250124
91 146 2232035
rchacko@cmcvellore.ac.in |
| Dr. Subodh Shivde |
Deenanath Mangeshkar Hospital |
Erandawne, Near Mhatre Bridge,-411004
Pune
MAHARASHTRA |
91-9822217380
91 22 24520104
shivdes@yahoo.co.in |
| Dr Rajeev Sood |
Dr. Ram Manohar Lohia Hospital and PGIMER, Room No. 31, OPD Block, |
,-110 001
New Delhi
DELHI |
919810005182
911123404323
drsoodr@yahoo.com |
| Dr. R K Shimpi |
Grant Medical Foundation, Ruby Hall Clinic |
40, Sassoon Road,,-411011
Pune
MAHARASHTRA |
91 9822059799
91 20 66019299
rkshimpi@vsnl.net |
| Dr. T P Sahoo |
Jawaharlal Nehru Cancer Hospital and Research Centre |
Idgah Hills, P B No 32,-462001
Bhopal
MADHYA PRADESH |
91-9893686246
91 755 2738325
tarini73@rediffmail.com |
| Dr. Sudhir Rawal |
Rajiv Gandhi Cancer Institute and Research Centre |
Sector ? 5, Rohini,-110085
New Delhi
DELHI |
91 9810139757
91 11 27931342
dr_rawal@yahoo.com |
| Dr. P.G. Jayaprakash |
Regional Cancer Centre |
Medical College Campus,-695001
|
91 9447043191
91 471 2447454
pgjprakash@yahoo.com |
| Dr. R. K. Chaudhary |
S P Medical College |
S P Medical College, Bikaner ,-334003
Bikaner
RAJASTHAN |
91 9414314294
91 151 2226329
drrkchaudhary@rediffmail.com |
| Dr. Anish Maru |
SEAROC Cancer Centre |
S.K Soni Hospital, Sect ? 5, Vidhyadhar Nagar,-302013
Jaipur
RAJASTHAN |
91 9829060128
91 141 2233337
anishmaru@yahoo.com |
| Dr. N.K.Mohanty |
V.M Medical College and Safdarjang Hospital, Sri Aurbindo Marg |
,-110 021
New Delhi
DELHI |
011-26190954
91 11 26190954
nayankm@yahoo.co.in |
| Dr. Kalyan Kumar Sarkar |
Woodlands Medical Centre |
915, Alipore Road,-700017
Kolkata
WEST BENGAL |
91 9830037314
91 33 24567090
kalyansarkar@vsnl.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 13 |
| Name of Committee |
Approval Status |
| Central Ethics Committee |
Approved |
| Dr. RML Hospital Ethics Committee |
Approved |
| Ethics Committee |
Approved |
| Ethics Committee |
Approved |
| Ethics Committee safdarjang hospital |
Approved |
| Ethics Committee, Poona Medical Research Foundation |
Approved |
| Ethics Committee, SP medical College and associated group of Hospitals, Bikaner |
Approved |
| Ethics Committee, Woodlands Medical Centre |
Approved |
| Human Ethics Committee, Regional Cancer Centre Thiruvananthpuram |
Approved |
| Institutional Ethical Committee, Jawahar Lal Nehru cancer Hospital and Research Centre |
Approved |
| Institutional Ethics Committee |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Center |
Approved |
| SEAROC Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Metastatic Hormone-resistant Prostate Cancer, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Docetaxel |
Docetaxel 75 mg/m2 administered intravenously (iv) over 1 hour on Day 1 of each 21-day cycle. |
| Intervention |
ZD4054 PLUS DOCATAXEL |
ZD4054 10 mg |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Day(s) |
| Age To |
99.00 Day(s) |
| Gender |
Male |
| Details |
For inclusion in the study patients must fulfil all of the following criteria:
1. Provision of informed consent
2. Male, aged 18 years or older. There is no upper limit for the age criteria.
3. Histological or cytological confirmation of adenocarcinoma of the prostate
4. Documented evidence of bone metastasis on bone scan. Patients must have disease involvement <75% of the spine, pelvis and ribs in the anteroposterior (AP) or posteroanterior (PA) view. Patients with ï‚£3 lesions seen on bone scan will require a CT scan, MRI or x-ray to confirm
5. Biochemical progression of prostate cancer, documented while the patient is castrate:
ï€ Biochemical progression is defined as at least 2 stepwise increases in PSA over a period of ≥1 month (values do not need to be consecutive but 2 values that have increased since the previous highest value are required) with at least 14 days between each measurement irrespective of assay or laboratory
ï€ Historical values may be used
ï€ The last PSA must be an increase of ≥50 % of the first PSA value of the 3 values or an absolute increase of ≥10 ng/mL over the initial PSA
ï€ The final PSA value must be ≥1.2 ng/mL in patients who have had a radical prostatectomy and ≥ 5ng/mL in all other patients
6. Surgically castrated or continuously medically castrated with serum testosterone ï‚£2.4 nmol/L (70 ng/dL).
7. World Health Organisation (WHO) performance status 0 ? 1 (see Appendix E).
8. Life expectancy of 3 months or more.
For inclusion in the genetic component of the study, patients must fulfil the following criterion:
1. Provision of informed consent for genetic research.
If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to participate
|
|
| ExclusionCriteria |
| Details |
Any of the following is regarded as a criterion for exclusion from the study:
1. Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment
2. Prior cytotoxic chemotherapy (such as paclitaxel, docetaxel and mitoxantrone) for the treatment of recurrent prostate cancer (prior estramustine therapy is allowed), as well as other targeted cancer therapies (such as EGF, EGFR, VEGF and VEGFR)
3. Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment
4. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone, St John?s Wort) within 2 weeks of starting study treatment. Dexamethasone is a known inducer of CYP2D6 and CYP3A4 but is acceptable for this study when used as part of the standard docetaxel regime
5. Use of systemic retinoids within 2 weeks of starting study treatment
6. Have received investigational drug in another clinical study of anti-cancer therapy, within 4 weeks of starting study treatment
7. Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists
8. Acute or evolving spinal cord compression or neurological symptoms or signs consistent with this. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed
9. Symptomatic peripheral neuropathy of CTCAE grade 2 or higher
10. Known or suspected central nervous system metastases.
11. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
12. Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification) or myocardial infarction within 6 months prior to study entry
13. QT interval corrected for heart rate eg, by Bazett?s correction >470 msec
14. Previous history or presence of another malignancy within the preceding 5 years except treated squamous/basal cell carcinoma of the skin
15. In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease, (eg, currently unstable or uncompensated respiratory, cardiac, hepatic or renal disease) or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
16. Absolute Neutrophil Count (ANC) <1.5 x 109/L (1,500/mm3); haemoglobin (Hb) 9 g/dL; platelet count <100 x 109/L (100,000/mm3). Concomitant use of erythropoietin or blood transfusions is allowed
17. Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert?s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician
18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastases
19. Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
20. Patients who discontinue after randomisation cannot be re-enrolled. Patients who fail to meet the inclusion/exclusion criteria may be reconsidered once for participation in the study. Patients who are re-enrolled must be re-consented and will be assigned a new enrolment number
21. Involvement in the planning and conduct of the study (applies to ICON and AstraZeneca staff or staff at the study site).
The following are regarded as an exclusion criteria for genetic research:
1. The patient has undergone a previous bone marrow transplant
2. The patient has undergone a whole blood transfusion in the preceding 90 days
|
|
Method of Generating Random Sequence
Modification(s)
|
Stratified randomization |
Method of Concealment
Modification(s)
|
Centralized |
Blinding/Masking
Modification(s)
|
Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| The primary objective of this study is to determine the effect of ZD4054 in combination with docetaxel on overall survival compared with docetaxel; overall survival defined as time to death (from randomisation) from any cause |
Primary Analysis at 508 patients deaths |
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
Assess the effect of ZD4054 in combination with docetaxel on progression free survival, on skeletal related events, on time to PSA progression, on time to pain progression, on pain response, on Health related Quality of Life, on PSA response.
Assess the safety & tolerability of ZD4054
|
Additional 12 month follow up for survival. |
|
Target Sample Size
Modification(s)
|
Total Sample Size="1044"
Sample Size from India="132"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 3 |
Date of First Enrollment (India)
Modification(s)
|
29/01/2008 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
01/10/2007 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="4"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
None |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This a Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer which will be conducted in approximately 1044 (522/arm) patients recruited from approximately 150 hospital-based centres globally with 13 sites in India. The primary objective of this study is to determine the effect of ZD4054 in combination with docetaxel on overall survival compared with docetaxel; overall survival defined as time to death (from randomisation) from any cause. Globally in this study till date 450 subjects have been randomized, In India till date 54 subjects have been randomized. The total target number of subjects proposed to be recruited in India is 93 randomized. |