A Clinical Trial Comparing Gemcitabine and Carboplatin With and Without P276-00 in Subjects With Metastatic Triple Negative Breast Cancer, With a Run-in of Escalating Dose of P276-00 Added to Gemcitabine and Carboplatin

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT01333137
First received: April 8, 2011
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

P276-00 is a novel, potent, small-molecule, flavone-derived Cdk 4 D1, Cdk1 B, and Cdk9 T inhibitor, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines.This study is planned to compare efficacy of the standard chemotherapy regimen of gemcitabine and carboplatin when administered with or without P276-00 in subjects with advanced triple negative breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Gemcitabine and Carboplatin
Drug: P276-00 along with Gemcitabine and carboplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Randomized Phase II Trial Comparing Gemcitabine and Carboplatin With and Without P276-00 in Subjects With Metastatic Triple Negative Breast Cancer, With a Phase I Run-in of Escalating Dose of P276-00 Added to Gemcitabine and Carboplatin

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • Median Progression free survival [ Time Frame: 1 year and above ] [ Designated as safety issue: No ]
    The primary efficacy endpoint will be median progression-free survival (PFS), defined as the time from the beginning of study treatment to the occurrence of documented disease progression or recurrence, or death from any cause


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
  • Overall survival at 6 months [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Progression Free Survival at 6 months [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: upto 3 years and above ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: upto 3 years and above ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: August 2011
Estimated Study Completion Date: April 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Gemcitabine and Carboplatin
Gemcitabine 1000 mg/m2/day on Days 1 & 8 and carboplatin at AUC 2 on Days 1 and 8 every 21 days.
Drug: Gemcitabine and Carboplatin
Gemcitabine 1000 mg/m2/day on Days 1 & 8 and carboplatin at AUC 2 on Days 1 and 8 every 21 days.
Experimental: P276-00 along with Gemcitabine and carboplatin
P276-00 will be administered at starting dose of 100 mg/m2/day (and higher if tolerated) in 200 mL of 5% dextrose as an iv infusion over 30 minutes, on Days 1 to 5, along with gemcitabine 1000 mg/m2/day and carboplatin at AUC 2 on Days 1 & 8 every 21 days.In Phase 2 component, P276-00 will be administered at recommended phase II dose of P276-00 in combination with standard dose of gemcitabine and carboplatin.
Drug: P276-00 along with Gemcitabine and carboplatin
In phase I run in period, P276 00 will be administered at starting dose of 100 mg/m2/day (and higher if tolerated) in 200 mL of 5% dextrose as an iv infusion over 30 minutes, on Days 1 to 5, along with gemcitabine 1000 mg/m2/day and carboplatin at AUC 2 on Days 1 & 8 every 21 days. In Phase 2 component, P276-00 will be administered at recommended phase II dose of P276-00 in combination with standard dose of gemcitabine and carboplatin.

  Eligibility

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

Inclusion Criteria:

  1. Females of age ≥18 years.
  2. Histologically documented metastatic triple negative breast cancer (any triple negative breast cancer for Phase I)
  3. Two or fewer chemotherapy regimens for advanced disease (no limit of prior regimens for Phase I)
  4. ECOG performance score of 1 or less
  5. Presence of measurable disease by RECIST 1.1 criteria (not for the Phase I portion)
  6. Ability to understand and the willingness to sign a written informed consent document (ICD)
  7. Full recovery from all prior treatment toxicities to Common Terminology Criteria for Adverse Events (CTCAE V.4) Grade ≤ 1

Exclusion Criteria:

  1. Prior chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration
  2. Prior radiation therapy within 6 weeks of study drug administration
  3. Subject with known active CNS metastases and/or carcinomatous meningitis. However, subjects with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases (2) off steroids that are used to minimize surrounding brain edema.
  4. Prior therapy with gemcitabine or a platinum agent (not for the Phase I part)
  5. Prior therapy with a Cdk/cyclin inhibitor or any flavones derivative
  6. QTc interval >450 msec (using Fridericia's formula)
  7. Any acute illness including uncontrolled diabetes, symptomatic or otherwise uncontrolled cardiac disease (coronary artery disease, arrhythmias, congestive heart failure) or other illness that in the judgment of the investigator would introduce additional medical risks
  8. Visceral crisis including extensive liver disease with>50% parenchymal involvement or lymphangitic pulmonary disease
  9. History of other prior malignancies except for properly treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, or in situ breast cancer
  10. Expected survival of less than 3 months
  11. Hemoglobin <9.0 gm/dL
  12. Absolute neutrophil count <1500/mm3
  13. Platelet count <100,000/mm3
  14. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 × institutional upper limit of normal (ULN)
  15. Total bilirubin, >1.5 × institutional ULN
  16. Serum creatinine >1.5 mg/dL
  17. Subjects with known infection with human immunodeficiency virus (HIV), tuberculosis, Hepatitis C or Hepatitis B
  18. Pregnant or lactating women
  19. Women of childbearing potential not willing to use approved methods of contraception after signing the ICD, during the entire study and for at least 4 weeks after completion of study or following withdrawal from the study

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01333137

Locations
United States, California
Disney Cancer Center
Burbank, California, United States
3855 Health Sciences Drive
La Jolla, California, United States, 92093
UC Davis Cancer Center
Sacramento, California, United States, 95817
United States, Missouri
Washington University
St. Louis, Missouri, United States
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Dr.Debasish Tripathy USC/Norris Comprehensive Cancer Center 1441 Eastlake Avenue, Rm 3440, Los Angeles, CA 90033
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT01333137     History of Changes
Other Study ID Numbers: P276-00/52/10
Study First Received: April 8, 2011
Last Updated: December 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Piramal Enterprises Limited:
Triple negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 16, 2014