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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

Phase 2
18 Years
Not Enrolling

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Trial Information

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

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.

Inclusion Criteria:

1. Subject with histologically confirmed stage III (unresectable) or stage IV metastatic
melanoma as per revised 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 IL-2

4. Subjects with measurable disease [at least one unidimensionally measurable lesion ³
20 mm with conventional techniques (CT, MRI, X-ray) or ³ 10 mm by spiral 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 ≥ 9 g/dL

- Absolute Neutrophil count ≥ 1,500/mm3

- Platelets ≥ 100,000/mm3

- Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN)

- AST/ALT ≤ 2.5 X institutional ULN or ≤ 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 CNS metastasis without evidence of recurrence for 12 week or more

- Brain metastasis treated by radiosurgery without evidence of recurrence or
progression for 12 week or more

- Multiple brain lesions treated with whole brain radiation therapy (WBRT) with
stable disease off corticosteroids for 12 week or more prior to start of therapy

10. Ability to understand and the willingness to sign a written informed consent

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 (AE ³ CTCAE Grade 2) due to agents
administered more than 4 week 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 > 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


Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival rate at Day 168

Outcome Time Frame:

168 days

Safety Issue:


Principal Investigator

Peter Hersey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Newcastle University


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

May 2009

Completion Date:

November 2012

Related Keywords:

  • Melanoma
  • metastatic malignant melanoma with cyclin D1 positivity
  • Melanoma