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

NCT01333137 | Terminated Phase 1 DMC

• 1 other identifier: P276-00/52/10
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Breast Cancer

Keywords

Triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Overall survival (OS)

  at 3 years

• Overall survival at 6 months

  at 6 months

• Progression Free Survival at 6 months

  at 6 months

• Objective response rate

  upto 3 years and above

• Duration of response

  upto 3 years and above

Study Arms (2)

Gemcitabine and Carboplatin

ACTIVE COMPARATOR

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

P276-00 along with Gemcitabine and carboplatin

EXPERIMENTAL

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

Interventions

Gemcitabine and Carboplatin DRUG

Gemcitabine 1000 mg/m2/day on Days 1 \& 8 and carboplatin at AUC 2 on Days 1 and 8 every 21 days.

Gemcitabine and Carboplatin

P276-00 along with Gemcitabine and carboplatin DRUG

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.

P276-00 along with Gemcitabine and carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration
• Prior radiation therapy within 6 weeks of study drug administration
• 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.
• Prior therapy with gemcitabine or a platinum agent (not for the Phase I part)
• Prior therapy with a Cdk/cyclin inhibitor or any flavones derivative
• QTc interval \>450 msec (using Fridericia's formula)
• 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
• Visceral crisis including extensive liver disease with\>50% parenchymal involvement or lymphangitic pulmonary disease
• 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
• Expected survival of less than 3 months
• Hemoglobin \<9.0 gm/dL
• Absolute neutrophil count \<1500/mm3
• Platelet count \<100,000/mm3
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>3 × institutional upper limit of normal (ULN)
• Total bilirubin, \>1.5 × institutional ULN

Sponsors & Collaborators

• Piramal Enterprises Limited: lead

Study Sites (4)

Disney Cancer Center

Burbank, California, United States

Location

3855 Health Sciences Drive

La Jolla, California, 92093, United States

Location

UC Davis Cancer Center

Sacramento, California, 95817, United States

Location

Washington University

St Louis, Missouri, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Dr.Debasish Tripathy

  USC/Norris Comprehensive Cancer Center 1441 Eastlake Avenue, Rm 3440, Los Angeles, CA 90033

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2011
• First Posted: April 11, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: March 1, 2014
• Last Updated: September 4, 2014

Record last verified: 2014-09

Locations

US (4)