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Open Label Phase I Study of P276-00 in Patients With Advanced Refractory Neoplasms

This study has been completed.
Sponsor:
Information provided by:
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00407498
First received: December 4, 2006
Last updated: December 31, 2008
Last verified: December 2008
  Purpose

P276-00 is specific Cdk4-D1 and Cdk1-B inhibitor. P276-00 exhibited significant tumour reduction in animal models with less adverse effects.Based on the results from various in-vitro studies, P276-00 could be a potential candidate as a new mechanism based drug for the treatment of cancer.This Phase I study will determine the Maximum Tolerated Dose,Dose Limiting Toxicity and efficacy of P 276-00 in patients with advanced Refractory neoplasms.


Condition Intervention Phase
Neoplasm
Drug: P276-00
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Multicentric Phase 1 Study of Selective Cyclin Dependent Kinase Inhibitor P276-00 in Patients With Advanced Refractory Neoplasms

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • To determine the maximum tolerated dose and dose limiting toxicity of selective Cdk inhibitor P276-00 in patients with advanced refractory neoplasms. [ Time Frame: DLT to be seen for cycle 1.Adverse events as and when they occur during the trial duration and till their resolution after exit from study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the toxic effects, pharmacokinetics and clinical response of this regimen. [ Time Frame: Pharmacokinetics on day 1 and 5 of cycle 1, clinical response after every 2 cycles, toxic effects of the drug as and when they occur to be evaluated ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: May 2005
Study Completion Date: September 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: P276-00
    Starting dose of 9 mg/m2/day from day 1to 5 and day 8 to 12 in 21 day cycle.Protocol wa amended to dose the subjects for day 1 to5 in 21 day cycle after 34.4 mg/m2/day cohort.Maximum dose administered was 259 mg/m2/day
  Eligibility

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

Inclusion Criteria:

  1. Patients must have histologically and/ or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
  2. Patients of either sex, of all races and ethnic groups, and > 18 years of age
  3. ECOG (Eastern Cooperative Oncology Group) performance status < 2
  4. Patients with life expectancy of at least 4 months.
  5. Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count ≥ 1,500/mL
    • platelets ≥ 100,000/mL
    • total bilirubin within normal institutional limits
    • AST/ALT ≤ 2.5 X institutional upper limit of normal (ULN)
    • creatinine within 1.5 times the upper normal institutional limits
  6. The effects of P276-00 on the developing human foetus are unknown. For this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study.
  7. Concomitant medications for diabetes, hypertension, pain relief and any other co-existing conditions, except cancer, are permitted when the patient is on study medication. There should be no change in the dosage of these medications in the 2 weeks prior to day 1 of cycle 1, with the exception of dosages for pain relief medication. Changes in the dose of anti-emetics and diuretics may be made provided they will not interfere with probable adverse effects of investigational product.
  8. Ability to understand and the willingness to sign a written informed consent document.
  9. Patients must have measurable disease.

Exclusion Criteria:

  1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study (date of consent); or patients who have not recovered from adverse events (except grade 1 toxicities) due to agents administered more than 4 weeks earlier.
  2. Patients having received any other investigational agents within 4 weeks prior to the date of consent and patients who have not recovered completely from the side effects of the earlier investigational agent.
  3. Patients with known brain metastases should be excluded from this clinical trial.
  4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to P276-00.
  5. Patients having history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months.
  6. Patients having diarrhoea requiring anti-diarrhoeal therapy.
  7. Patients with uncontrolled and unstable intercurrent illness.
  8. Women who are pregnant or nursing. P276-00 may have the potential for teratogenic or abortifacient effects. Since there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with P276-00, breastfeeding should be discontinued if the mother is to be treated with P276-00.
  9. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients are excluded from the study.
  10. Patients requiring the use of concomitant medications that prolong the QT/QTc interval and /or are known to cause Torsades de Pointes (TdP)
  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: NCT00407498

Locations
Canada, Ontario
Juravinsky Cancer Centre
Hamilton, Ontario, Canada, L8V5C2
Kingston General Hospital
Kingston, Ontario, Canada, K7L 2V7
India
Nizam's Institute of Medicai Sciences
Hyderabaad, Andhrapradesh, India, 500082
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Hal Hirte, MD, FRCP Juravinsky Cancer Centre
Principal Investigator: Tara Baetz, MD, FRCP Kingston General Hospital
Principal Investigator: Raghunadharao D, MD, DM Nizam's Institute of Medicai Sciences
  More Information

Publications:
Hirte H.W, Raghunatharao D, Baetz S, Hotte J, Rajappa S, Iaccobucci A, Sharma S, Parikh H, Kulkarni S, Patil S, Padigaru M, Gaston S. A Phase I study of the selective cyclin dependant kinase inhibitor P276-00 in Patients with advanced refractory neoplasms. AACR 2007 Abstract number #802

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Himanshu Parikh, Nicholas Piramal India Limited
ClinicalTrials.gov Identifier: NCT00407498     History of Changes
Other Study ID Numbers: P276-00/01/04
Study First Received: December 4, 2006
Last Updated: December 31, 2008
Health Authority: Canada: Health Canada
India: Ministry of Health

Keywords provided by Piramal Enterprises Limited:
P 276-00
Advanced Refractory Neoplasm
Maximum Tolerated Dose
Dose Limiting Toxicity
Pharmacokinetics

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

ClinicalTrials.gov processed this record on November 20, 2014