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

September 3, 2014 updated by: Piramal Enterprises Limited

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Burbank, California, United States
        • Disney Cancer Center
      • La Jolla, California, United States, 92093
        • 3855 Health Sciences Drive
      • Sacramento, California, United States, 95817
        • UC Davis Cancer Center
    • Missouri
      • St. Louis, Missouri, United States
        • Washington University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression free survival
Time Frame: 1 year and above
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
1 year and above

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: at 3 years
at 3 years
Overall survival at 6 months
Time Frame: at 6 months
at 6 months
Progression Free Survival at 6 months
Time Frame: at 6 months
at 6 months
Objective response rate
Time Frame: upto 3 years and above
upto 3 years and above
Duration of response
Time Frame: upto 3 years and above
upto 3 years and above

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dr.Debasish Tripathy, USC/Norris Comprehensive Cancer Center 1441 Eastlake Avenue, Rm 3440, Los Angeles, CA 90033

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

April 8, 2011

First Submitted That Met QC Criteria

April 8, 2011

First Posted (Estimate)

April 11, 2011

Study Record Updates

Last Update Posted (Estimate)

September 4, 2014

Last Update Submitted That Met QC Criteria

September 3, 2014

Last Verified

September 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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