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

Neoplasm Clinical Trial

Official title:

An Open Label Multicentric Phase 1 Study of Selective Cyclin Dependent Kinase Inhibitor P276-00 in Patients With Advanced Refractory Neoplasms

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00408018
• Other study ID #: P276-00/02/05
• Status: Terminated
• Phase: Phase 1
• First received: December 4, 2006
• Last updated: December 31, 2008
• Start date: March 2006
• Est. completion date: October 2008

Study information

• Verified date: December 2008
• Source: Piramal Enterprises Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: October 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Neoplasm
• Neoplasms

Intervention

Drug:
• P276-00
Potent Cyclin dependent kinase (cdk) cdk4 D1, cdk1 B and cdk9 T inhibitor

Locations

Country	Name	City	State
India	Nizam's Institute of Medicai Sciences	Hyderabaad	Andhra Pradesh
India	Global Hospital	Hyderabad	Andhra Pradesh
India	Tata Memorial Hospital	Mumbai	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Piramal Enterprises Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety assessment by Laboratory investigations (Hematology,Biochemistry, urinalysis), ECG, Holter monitoring,Physical examination		2 years	Yes
Secondary	Tumor measurements,Pharmacokinetics, MALDI- TOF to study plasma peptide pattern		2 years	No