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Trial registered on ANZCTR


Registration number
ACTRN12609000815268
Ethics application status
Approved
Date submitted
2/06/2009
Date registered
18/09/2009
Date last updated
19/02/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy Study Of P276-00 In Subjects Of Malignant Melanoma Positive For Cyclin D1 Expression (ENVER)
Scientific title
An Open Label, Multicentre, Two Stage, Phase II Study To Evaluate Efficacy And Safety Of P276-00 In Subjects Of Malignant Melanoma Positive For Cyclin D1 Expression
Secondary ID [1] 910 0
registered ClinicalTrials.gov ID NCT00835419
Universal Trial Number (UTN)
Trial acronym
ENVER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 236902 0
Condition category
Condition code
Cancer 237254 237254 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
P276-00 is a novel potent small molecule flavone derived Cyclin dependent kinase (Cdk) Cdk 4-D1, Cdk1-B and Cdk9-T inhibitor.

185 mg/ml2 of P276-00 (in 200 mL of 5% Dextrose) will be administered once daily to participants by intravenous (i.v.) infusion over 30 minutes from day 1 to day 5 of each 21-day cycle until objective or clinical evidence of progression of disease or occurrence of an unacceptable toxicity.
Intervention code [1] 236688 0
Treatment: Drugs
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 238068 0
Progression Free Survival rate (using Response Evaluation Criteria In Solid Tumours (RECIST) criteria) at Day 168
Timepoint [1] 238068 0
Time Frame: 168 days following commencement of treatment.

Tumour measurements will be undertaken via Computed Tomography (CT) scan at screening, at the end of every two cycles of treatment (6 weekly), at the end of study visit and at the 4 week follow-up visit.
Secondary outcome [1] 242260 0
Overall survival rate at 1 year (all cause mortality assessed through medical records)
Timepoint [1] 242260 0
Time Frame: 1 year following commencement of treatment
Secondary outcome [2] 257657 0
Objective response rate (via RECIST criteria)
Timepoint [2] 257657 0
Timeframe: Tumour measurements will be undertaken to assess objective response rate via CT scan at screening, at the end of every two cycles of treatment (6 weekly), at the end of study visit and at the 4 week follow-up visit.
Secondary outcome [3] 257658 0
Duration of response (via RECIST criteria)
Timepoint [3] 257658 0
Timeframe: Tumour measurements will be undertaken to assess duration of response via CT scan at screening, at the end of every two cycles of treatment (6 weekly), at the end of study visit and at the 4 week follow-up visit.

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. Subject with histologically confirmed stage III (unresectable) or stage IV metastatic melanoma as per revised American Joint Committee On Cancer (AJCC) melanoma staging
2. Subject positive for cyclin D1 expression by appropriate technique
3. Subject with at least one metastasis in which surgery was not a curative option and had relapsed from, or had not responded to at least one regimen containing Dacarbazine and or Interleukin (IL)-2
4. Subjects with measurable disease [at least one unidimensionally measurable lesion greater than or equal to 20 mm with conventional techniques (Computed Tomography (CT), Magnetic Resonance Imaging (MRI), X-ray) or greater than or equal to 10 mm by spiral (Computed Tomography (CT) scan]
5. Subject of either sex and 18 years of age or elder
6. Eastern Cooperative Oncology Group (ECOG) performance status 2 or less
7. Subject with life expectancy of at least 4 months
8. Subject must have normal organ and marrow function as defined below
- Hemoglobin greater than or equal to 9 g/dL
- Absolute Neutrophil count greater than or equal to 1,500/mm3
- Platelets greater than or equal to 100,000/mm3
- Total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)
- Aspartate Amino Transferase (AST)/ Alanine Amino Transferase (ALT) less than or equal to 2.5 X institutional upper limit of normal (ULN) or less than or equal to 5 X ULN if liver function abnormalities are due to underlying malignancy
- S. creatinine within 1.5 times the upper normal institutional limits
9. Subjects with metastatic disease to the central nervous system will be included provided they had either:
- No evidence of leptomeningeal disease
- Resected central nervous system (CNS) metastasis without evidence of recurrence for 12 week or more
- Brain metastasis treated by radiosurgery without evidence of recurrence or progression for 12 weeks or more
- Multiple brain lesions treated with whole brain radiation therapy (WBRT) with stable disease off corticosteroids for 12 weeks or more prior to start of therapy
10. Ability to understand and the willingness to sign a written informed consent document.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treatment with P276-00 or other cyclin dependent kinase (CDK) targeting agents anytime in the past
2. History of allergic reactions attributed to compounds of chemical composition similar to P276-00
3. Subject who have had chemotherapy, immunotherapy or radiotherapy within 4 week prior to first dosing of study agent. For nitrosoureas, there shall be interval of at least six week from first dosing of study agent
4. Subject who have not recovered from adverse events (adverse event (AE) greater than or equal to Common Terminology Criteria for Adverse Event (CTCAE) Grade 2) due to agents administered more than 4 weeks earlier.
5. Subject who had received any other investigational drug within 1 month prior to day 1 of study drug administration
6. Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or any other cancer for which the subject has been disease-free for at least 3 years
7. Any medical condition (such as but not limited to severe/unstable angina, history of myocardial infarction, coronary/peripheral artery bypass graft, symptomatic congestive cardiac failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism) or laboratory abnormality(ies) which might make it difficult for the subject to participate in the study, at the discretion of the Principal Investigator (PI)or co-PI
8. Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness
9. QTc greater than 470 millisecond on 12 lead Electrocardiogram at screening
10. Pregnant or nursing women
11. Women of childbearing potential [defined as a sexually mature woman who has not undergone hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e. who has had menses any time in the preceding 24 consecutive months)] and men, not agreeing to use adequate contraception (e.g., hormonal or barrier method of birth control or abstinence) after signing an informed consent document (ICD), during the duration of study participation and for at least 4 week after withdrawal from the study, unless they are surgically sterilized

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment postcode(s) [1] 1782 0
2298
Recruitment postcode(s) [2] 1783 0
2145
Recruitment postcode(s) [3] 1784 0
2500
Recruitment postcode(s) [4] 1785 0
2640
Recruitment postcode(s) [5] 1786 0
3058
Recruitment postcode(s) [6] 1787 0
3199
Recruitment postcode(s) [7] 1788 0
4101
Recruitment outside Australia
Country [1] 1823 0
New Zealand
State/province [1] 1823 0
Christchurch

Funding & Sponsors
Funding source category [1] 5078 0
Commercial sector/Industry
Name [1] 5078 0
Piramal Life Sciences Limited
Address [1] 5078 0
1, Nirlon Complex, Off Western Express Highway, Near NSE Complex, Goregaon (East), Mumbai 400 063, India
Country [1] 5078 0
India
Primary sponsor type
Commercial sector/Industry
Name
Piramal Enterprises Limited
Address
Piramal Enterprises Limited, Nirlon Complex Off Western Express Highway, Near NSE Complex, Goregaon (East), Mumbai 400 063
Country
India
Secondary sponsor category [1] 4583 0
Commercial sector/Industry
Name [1] 4583 0
INCResearch Australia Pty. Ltd.
Address [1] 4583 0
159 Port Road Hindmarsh, South Australia, 5007, Australia
Country [1] 4583 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239177 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 239177 0
Locked Bag 1 Lookout Road
NEW LAMBTON
NSW 2305
Ethics committee country [1] 239177 0
Australia
Date submitted for ethics approval [1] 239177 0
Approval date [1] 239177 0
28/04/2009
Ethics approval number [1] 239177 0
09/02/18/3.05
Ethics committee name [2] 239178 0
Bellbery Human Research Ethics Committee
Ethics committee address [2] 239178 0
229 Greenhill Road
Dulwich SA 5065
Ethics committee country [2] 239178 0
Australia
Date submitted for ethics approval [2] 239178 0
Approval date [2] 239178 0
Ethics approval number [2] 239178 0
A20/09A
Ethics committee name [3] 239180 0
Joint Hospitals Ethics Committee
Ethics committee address [3] 239180 0
Vermont Street,
Wodonga
Vic 3689
Ethics committee country [3] 239180 0
Australia
Date submitted for ethics approval [3] 239180 0
Approval date [3] 239180 0
Ethics approval number [3] 239180 0
JHEC:324/09/2
Ethics committee name [4] 290598 0
Mater Health Services Human Research Ethics Committee
Ethics committee address [4] 290598 0
Raymond Terrace, South Brisbane, Queensland, 4101
Ethics committee country [4] 290598 0
Australia
Date submitted for ethics approval [4] 290598 0
Approval date [4] 290598 0
28/09/2009
Ethics approval number [4] 290598 0

Summary
Brief summary
Currently, melanoma is the fifth most common cancer diagnosed in men and the seventh most common cancer diagnosed in women.Advanced melanoma has a very poor prognosis.For a vast majority of subjects with malignant melanoma, there are no effective therapies.Therefore, the development of effective therapies for this subject population remains a priority in oncology.In a limited study in melanomas, increased cyclin D1 protein expression, as was observed in 33% cases.P276-00 is a novel potent small molecule flavone derived Cyclin dependent kinase (Cdk) Cdk 4-D1, Cdk1-B and Cdk9-T inhibitor.P276-00 demonstrated significant and selective antiproliferative effect against melanoma cell lines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29682 0
Prof Peter Hersey
Address 29682 0
Newcastle Melanoma Unit Calvary Mater Newcastle Corner Edith and Platt Streets Waratah NSW 2298
Country 29682 0
Australia
Phone 29682 0
+61 (0)2 4923-6828
Fax 29682 0
+61 (0)2 4923-6184
Email 29682 0
Peter.Hersey@newcastle.edu.au
Contact person for public queries
Name 12929 0
Ms Laura Johnston
Address 12929 0
INCResearch Australia Pty. Ltd., Suite 1, Level 2, 924 Pacific Highway Gordon NSW 2072
Country 12929 0
Australia
Phone 12929 0
+61 (0)414 480 069
Fax 12929 0
+61 (0)7 3848-802
Email 12929 0
laura.johnston@incresearch.com
Contact person for scientific queries
Name 3857 0
Dr David Fuller
Address 3857 0
INCResearch Australia Pty. Ltd., Suite 1, Level 2, 924 Pacific Highway Gordon NSW 2072
Country 3857 0
Australia
Phone 3857 0
+61 (0)2 8437 9238
Fax 3857 0
+61 (0)2 8437 9299
Email 3857 0
david.fuller@incresearch.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary