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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00772876
First received: October 13, 2008
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: P1446A-05
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter Phase I Study Of Selective Cyclin Dependent Kinase Inhibitor P1446A-05 In Subjects With Advanced Refractory Malignancies

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • Number of Dose Limiting Toxicities at a dose level [ Time Frame: Cycle 1 of each subject ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: At the end of every 2 cycles ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: December 2008
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P1446A-05
Single arm of the study drug. This being a dose escalation study, patient will receive a dose depending on the stage of the trial.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772876

Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T4N4N2
Cross Cancer Institute (CCI),
Edmonton,, Alberta, Canada, T6G 1Z2
Canada, British Columbia
British Columbia Cancer Agency (BCCA),
Vancouver,, British Columbia, Canada, BC V5Z 4E6
Canada, Ontario
London Health Sciences Centre (LHSC)
London, Ontario, Canada, ON N6A 4L6
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Siu-Chung Q Chu, MD, FRCP(C) Staff Medical Oncologist, Cross Cancer Institute, Department of Medical Oncology, Edmonton, AB
Principal Investigator: Christian K Kollmannsberger, MD Medical Oncologist, Division Medical Oncology, British Columbia Cancer Agency (BCCA), Vancouver, BC
Principal Investigator: S Welch London Health Sciences Centre (LHSC), London, Ontario
Principal Investigator: Dr. Patricia Tang Tom Baker Cancer Centre, Calgary, Alberta
  More Information

No publications provided by Piramal Enterprises Limited

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT00772876     History of Changes
Other Study ID Numbers: P1446A-05/20/08
Study First Received: October 13, 2008
Last Updated: November 21, 2012
Health Authority: Canada: Health Canada
India: Drugs Controller General of India

Keywords provided by Piramal Enterprises Limited:
P1446A-05
Advanced refractory malignancies
Phase I

Additional relevant MeSH terms:
Neoplasms
Cyclin-Dependent Kinase Inhibitor Proteins
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014