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

This study has been terminated.
(The decision to terminate this study after 202 mg/m2 cohort was taken as MTD achieved in other study at 185 mg/m2)
Sponsor:
Information provided by:
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00408018
First received: December 4, 2006
Last updated: December 31, 2008
Last verified: December 2008
  Purpose

P276-00 is a molecule derived from Rohitukine, which through pre clinical assays was identified as a selective Cdk4-D1 and Cdk1-B inhibitor.The inhibition of these Cdks causes cell cycle arrest between the G1-S transition thus blocking the cell cycle events at an early stage of development. It therefore has the potential for being efficacious with lesser side effects.


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:
  • Safety assessment by Laboratory investigations (Hematology,Biochemistry, urinalysis), ECG, Holter monitoring,Physical examination [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor measurements,Pharmacokinetics, MALDI- TOF to study plasma peptide pattern [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: March 2006
Study Completion Date: October 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: P276-00
    Potent Cyclin dependent kinase (cdk) cdk4 D1, cdk1 B and cdk9 T inhibitor
  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:

    • Hemoglobin ≥10 gm/dL
    • 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) for the duration of the study during the duration of study participation and for at least 4 weeks after withdrawal from the study.
  7. Women who are nursing should not be included into the study
  8. 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.
  9. Ability to understand and the willingness to sign a written informed consent document.

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 diarrhea requiring anti-diarrheal therapy.
  7. Patients having coagulopathy requiring anticoagulation.
  8. Patients with uncontrolled but stable intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  9. 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.
  10. 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.
  11. 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00408018

Locations
India
Nizam's Institute of Medicai Sciences
Hyderabaad, Andhra Pradesh, India, 500082
Global Hospital
Hyderabad, Andhra Pradesh, India
Tata Memorial Hospital
Mumbai, Maharashtra, India, 400012
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Purvish M parikh, MD, DNB, PhD Tata Memorial Hospital
Principal Investigator: Raghunadharao D, MD, DM Nizam's Institute of Medical Sciences
Principal Investigator: Ravikumar Saxena, MD Global Hospital
  More Information

No publications provided

Responsible Party: Dr Himanshu Parikh, Piramal Life Sciences Limited
ClinicalTrials.gov Identifier: NCT00408018     History of Changes
Other Study ID Numbers: P276-00/02/05
Study First Received: December 4, 2006
Last Updated: December 31, 2008
Health Authority: India: Ministry of Health

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 April 23, 2014