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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01333137
• Other study ID #: P276-00/52/10
• Status: Terminated
• Phase: Phase 1
• First received: April 8, 2011
• Last updated: September 3, 2014
• Start date: August 2011
• Est. completion date: March 2014

Study information

• Verified date: September 2014
• Source: Piramal Enterprises Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: March 2014
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Disney Cancer Center	Burbank	California
United States	3855 Health Sciences Drive	La Jolla	California
United States	UC Davis Cancer Center	Sacramento	California
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Piramal Enterprises Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Progression free survival	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	No
Secondary	Overall survival (OS)		at 3 years	No
Secondary	Overall survival at 6 months		at 6 months	No
Secondary	Progression Free Survival at 6 months		at 6 months	No
Secondary	Objective response rate		upto 3 years and above	No
Secondary	Duration of response		upto 3 years and above	No