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

NCT ID: NCT00407498

Last Updated: 2009-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2008-09-30

Brief Summary

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.

Conditions

Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Piramal Enterprises Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Nicholas Piramal India Limited

Principal Investigators

Hal Hirte, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Juravinsky Cancer Centre

Tara Baetz, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Kingston Health Sciences Centre

Raghunadharao D, MD, DM

Role: PRINCIPAL_INVESTIGATOR

Nizam's Institute of Medicai Sciences

Locations

Juravinsky Cancer Centre

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

Nizam's Institute of Medicai Sciences

Hyderabaad, Andhrapradesh, India

Countries

Canada; India

References

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

Reference Type: RESULT

Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.

Reference Type: DERIVED

PMID: 19238148 (View on PubMed)

Other Identifiers

P276-00/01/04

Identifier Type: -

Identifier Source: org_study_id