Efficacy Study Of P276-00 In Subjects Of Malignant Melanoma Positive For Cyclin D1 Expression (ENVER)
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
Piramal Enterprises Limited
36 participants
Sep 10, 2009
Interventional
Conditions
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.
Eligibility
Inclusion Criteria20
- Subject with histologically confirmed stage III (unresectable) or stage IV metastatic melanoma as per revised American Joint Committee On Cancer (AJCC) melanoma staging
- Subject positive for cyclin D1 expression by appropriate technique
- 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
- 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]
- Subject of either sex and 18 years of age or elder
- Eastern Cooperative Oncology Group (ECOG) performance status 2 or less
- Subject with life expectancy of at least 4 months
- 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
- 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
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria11
- Treatment with P276-00 or other cyclin dependent kinase (CDK) targeting agents anytime in the past
- History of allergic reactions attributed to compounds of chemical composition similar to P276-00
- 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
- 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.
- Subject who had received any other investigational drug within 1 month prior to day 1 of study drug administration
- 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
- 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
- Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness
- QTc greater than 470 millisecond on 12 lead Electrocardiogram at screening
- Pregnant or nursing women
- 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
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Interventions
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.
Locations(1)
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ACTRN12609000815268