A Multicenter Phase I Clinical Study of a New Compound P1446A-05 in Patients With Advanced Refractory Malignancies

Cancer Clinical Trial

Official title:

An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00772876
• Other study ID #: P1446A-05/20/08
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2008
• Last updated: November 21, 2012
• Start date: December 2008
• Est. completion date: May 2012

Study information

• Verified date: November 2012
• Source: Piramal Enterprises Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaIndia: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

This is a phase I study of a novel compound P1446A-05. Aim of this study is to identify the the recommended phase II dose of the drug and to determine the nature of adverse effects associated with the drug. P1446A-05 capsules will be given continuously (28 days in each 28 day cycle) to patients suffering from advanced malignancies with no effective treatment available. The dose of the study agent will be lower i.e. 75 mg per day for initial patients. If this dose is found safe, higher dose will be administered to next set of (three to six) patients. This will continued till the safest and best dose is identified. Treatment will be given for 4 cycles and continued further if found effective. Dose schedule may be modified to introduce treatment holiday,if frequent adverse effects are seen on continuous administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: May 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and/ or cytologically confirmed solid malignant tumor or Malignant Lymphoma (excluding CNS Lymphoma and multiple myeloma) that is refractory to currently available treatment or for which no standard treatment exists

• Measurable disease

• Must have completed any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin C; 3 months for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before study entry and subjects must have recovered (to =grade 1) from the toxic effects from any prior therapy.

• Must not have had more than 40% of their bone marrow radiated and must have either measurable disease outside the field or progression post radiation therapy.

• Age = 18 years

• ECOG performance status = 2

• Life expectancy of at least 12 weeks

• Normal organ and marrow function as defined below:

Hemoglobin >/= 90 g/L Leukocytes >/=3 x 109/L Absolute Neutrophil Count (ANC) >/=1.5 x 109/L Platelets >/=100 x 109/L Total bilirubin </= 1.5 X institutional Upper Limit of Normal (ULN) AST(SGOT) </=2.5 X institutional ULN ALT(SGPT) </=2.5 X institutional ULN Creatinine </=1.5 X institutional ULN

• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• autologous or allogeneic bone marrow transplant within 6 months of day 1 of study drug administration

• Known brain metastases at the time of screening

• Any other investigational drug within 1 month prior to day 1 of study drug administration or not recovered (to =grade 1) from adverse effects of the investigational agent received prior to this period.

• History of allergic reactions attributed to compounds of similar chemical structure to P1446A-05.

• On immunosuppressive therapy.

• History of unstable angina or myocardial infarction or stroke within 6 months prior to Day 1 of study drug administration.

• Uncontrolled inter-current illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B.

• Pregnant or lactating 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 (two methods of contraception, including at least one barrier method, - i.e. : hormonal and a barrier method of birth control or abstinence) prior to study entry (after signing the informed consent document), during the duration of study participation and for at least 4 weeks after withdrawal from the study drug, unless they are surgically sterilised.

• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at an unacceptable risk or deems the subject not suitable for participation in the study.

Study Design

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• P1446A-05
P1446A-05 capsules will be given once daily for 28 days in each 28 day cycle for 4 such cycles. The starting dose, for first cohort will be 75 mg once daily. Subsequent cohorts of patients will receive higher doses till the recommended phase II dose is identified.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute (CCI),	Edmonton,	Alberta
Canada	London Health Sciences Centre (LHSC)	London	Ontario
Canada	British Columbia Cancer Agency (BCCA),	Vancouver,	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Piramal Enterprises Limited

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Dose Limiting Toxicities at a dose level		Cycle 1 of each subject	Yes
Secondary	Response rate		At the end of every 2 cycles	No