Clinical Trial: Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Phase Ib/II Trial of Taselisib (GDC-0032), a PI3K Inhibitor, in Combination With Enzalutamide in Patients With Androgen Receptor Positive Triple Negative Metastatic Brea

Brief Summary: This partially randomized phase Ib/II trial studies the side effects and best dose of taselisib when given together with enzalutamide and to see how well they work in treating patients with androgen receptor positive triple-negative breast cancer that has spread to other places in the body. Taselisib is a PI3K inhibitor. The PI3K pathway is involved is cancer growth. Androgen may cause the growth of tumor cells. Enzalutamide may stop the growth of tumor cells by blocking the androgen receptor from working. Giving taselisib with enzalutamide may be a better treatment for patients with breast cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of taselisib given in combination with enzalutamide: Assessment of dose limiting toxicities (DLTs) during the first 4 weeks of treatment (cycle 1). (Phase Ib) II. To determine the safety and tolerability of taselisib given in combination with enzalutamide: Determination of the maximally tolerated dose (MTD) of taselisib given in combination with enzalutamide. (Phase Ib) III. To evaluate the efficacy, as measured by clinical benefit rate (CBR), of enzalutamide + taselisib in patients with androgen receptor positive (AR+) triple negative (TN) metastatic breast cancer (MBC). (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival (PFS) of enzalutamide + taselisib in patients with AR+ TN MBC.

II. To assess the pharmacokinetics (PKs) of taselisib and enzalutamide in patients with AR+ TN MBC.

TERTIARY OBJECTIVES:

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

II. Levels of phosphatase and tensin homolog (PTEN) expression by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qPCR).

III. Presence of mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene.

IV. Human epidermal growth factor receptor 2 (HER2) (IHC, fluorescence in situ hybridization [FISH]) and estrogen receptor (ER)/progesterone receptor (PR) levels (IHC) in tum
Sponsor: Vanderbilt-Ingram Cancer Center

Current Primary Outcome:

  • Clinical Benefit Rate (CBR) - Phase II [ Time Frame: At 16 weeks ]
    CBR is defined as the proportion of patients with a best response of complete response (CR), partial response (PR), or (SD) stable disease. This will be studied using a Simon two-stage design.
  • Maximum Tolerated Dose (MTD) - Phase I [ Time Frame: 4 weeks ]
    defined as the highest dose tested in which a dose limiting toxicity is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels. Dose limiting toxicity will be graded according to the National Cancer Institute CTCAE version 4.0.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Overall Progression-Free Survival (PFS) [ Time Frame: Time from course 1, day 1 until objective tumor progression, assessed up to 3 years ]
    The overall PFS data for the patients at the dose recommended for phase II will be estimated using the Kaplan-Meier method with 95% confidence intervals.
  • Overall response rate (ORR) [ Time Frame: Up to 3 years ]
    The ORR and corresponding 95% confidence intervals will be calculated at the dose recommended for phase II.
  • Cmax, the peak plasma concentration of taselisib after administration of taselisib [ Time Frame: 0-4 hours pre-dose and 1, 3, and 6 hours post-administration (course 1, day 8 of phase Ib) ]
    Plasma samples may be used for exploratory analysis to evaluate potential taselisib-related metabolites and/or exploratory biomarker development.
  • Cmax, the peak plasma concentration of taselisib and enzalutamide after administration of both drugs [ Time Frame: 0-4 hours (hrs) pre-dose, 1, 3, and 6 hrs post-administration (course 2, day 15); 0-4 hrs pre-dose, 3 hrs post-administration (course 4, day 1), 0-4 hrs pre-dose, 2-4 hrs post administration (course 1, day 8, course 2 day 15, course 4 day 1 of phase II) ]
    Plasma samples may be used for exploratory analysis to evaluate potential taselisib-related metabolites and/or exploratory biomarker development.


Original Secondary Outcome: Same as current

Information By: Vanderbilt-Ingram Cancer Center

Dates:
Date Received: May 21, 2015
Date Started: June 2015
Date Completion:
Last Updated: January 9, 2017
Last Verified: January 2017