Clinical Trial: GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase Ib/II Trial of GDC-0941 (a PI3K Inhibitor) in Combination With Cisplatin in Patients With Androgen Receptor Negative Triple Negative Metastatic Breast Cancer

Brief Summary: This phase I/II trial study evaluates the tolerability and best tolerated dose of the PI3K inhibitor GDC-0941 when given with the chemotherapy cisplatin. This study will also examine how well the combination of GDC-0941 and cisplatin work in treating patients with androgen receptor negative triple negative metastatic breast cancer. Patients will be randomized to receive cisplatin alone or cisplatin with GDC-0941 in the phase II portion. Those receiving cisplatin alone can receive GDC-0941 upon progression of their disease. Cisplatin is a chemotherapy which has been shown to be effective in treating triple negative breast cancer. Preclinical studies show that adding a PI3K inhibitor such as GDC-0941 to cisplatin may be a more effective treatment for breast cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of GDC-0941 when given in combination with cisplatin in patients with androgen receptor-negative (AR-) triple negative (TN) metastatic breast cancer (MBC): assessment of dose limiting toxicities (DLTs) during the first 4 weeks of treatment (cycle 1); determination of the maximally tolerated dose (MTD) and recommended phase II dose of GDC-0941 given in combination with cisplatin. (Phase IB)

II. To evaluate the efficacy, as measured by the overall response rate (ORR), of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the clinical benefit rate (CBR) of cisplatin + GDC-0941 in patients with AR- TN MBC.

II. To determine the time to disease progression (TTP) of cisplatin + GDC-0941 versus cisplatin alone in patients with AR- TN MBC.

TERTIARY OBJECTIVES:

I. To characterize pharmacokinetics of GDC-0941 when administered in combination with cisplatin.

II. To explore predictors of response and mechanisms of resistance based on exploratory analysis of tumor tissue obtained through biopsies.

III. To assess the prognostic effects of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations and phosphatase and tensin homolog (PTEN) loss on TTP and CBR.

OUTLINE: This is a phase I, dose-deescalation study of PI3K inhibitor GDC-0941 followed by a randomized phase II study.

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Sponsor: Vanderbilt-Ingram Cancer Center

Current Primary Outcome:

  • Maximum Tolerated Dose(MTD) of GDC-0941 - (Phase Ib) [ Time Frame: 4 weeks ]
    MTD is defined as the highest dose tested in which a dose limiting toxicity (DLT)is experienced by 0 to 1, out of 6 patients among the dose levels assessed using CTCAE version 4.0
  • Percentage of Patients Achieving Overall Response Rate - (Phase II) [ Time Frame: at 8 weeks ]
    Overall response rate (ORR) is complete response (CR) + partial response (PR) measured by RECIST version 1.1


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of patients with dose-limiting toxicities per grade (DLT) - (Phase Ib) [ Time Frame: During the first 4 weeks ]
    Number of patients with Grade 3 and 4 toxicities per NCI Common Terminology for Adverse Events (CTCAE) version 4.0.
  • Clinical Benefit Ratio (CBR) [ Time Frame: at 32 weeks ]
    CBR is the corresponding 95% confidence interval at the MTD dose recommended for phase II. Defined as the number of patients with CR + PR + stable disease (SD) for 6 months
  • Time to Progression (TTP) [ Time Frame: From time of randomization to disease progression, up to 104 weeks ]
    TTP is calculated with the corresponding 95% confidence interval at the dose recommended for phase II. It is defined as the duration from randomization to objective tumor progression


Original Secondary Outcome: Same as current

Information By: Vanderbilt-Ingram Cancer Center

Dates:
Date Received: July 25, 2013
Date Started: September 2013
Date Completion:
Last Updated: August 17, 2015
Last Verified: August 2015