Clinical Trial: TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1 Study of MLN0128 and Bevacizumab in Patients With Recurrent Glioblastoma and Other Solid Tumors

Brief Summary: This phase I trial studies the side effects and best dose of raptor/rictor-mammalian target of rapamycin (mTOR) (TORC1/2) inhibitor MLN0128 when given in combination with bevacizumab in treating patients with glioblastoma, a type of brain tumor, or a solid tumor that has spread and not responded to standard treatment. TORC1/2 inhibitor MLN0128 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the progression of tumors by blocking the growth of new blood vessels necessary for tumor growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and recommended phase 2 dose (MTD/RP2D) of daily oral MLN0128 (TORC1/2 inhibitor INK128) when administered with bevacizumab in patients with advanced solid tumors including recurrent glioblastoma (GBM).

II. To evaluate the overall safety and tolerability of the combination of MLN0128 and bevacizumab.

SECONDARY OBJECTIVES:

I. To assess the preliminary anti-tumor activity of the combination of MLN0128 and bevacizumab, as determined by response rate (RR), progression-free survival (PFS) and overall survival (OS).

II. To assess tolerability throughout study therapy with MLN0128 and bevacizumab, including beyond the MTD interval with the following measures of cumulative treatment-related toxicities: frequency of toxicities leading to missed doses or delays; percentage of cycles given or not within 7 days of their scheduled times; percentage of actual planned dosage administration; percentage of patients that discontinue study drugs due to treatment related toxicity.

TERTIARY OBJECTIVES:

I. To assess cerebrospinal fluid (CSF) penetration of MLN0128 in combination with bevacizumab in patients with recurrent GBM by evaluating the plasma and CSF concentrations of MLN0128 in the absence and presence of bevacizumab.

II. To perform archival tumor analysis for markers of dysregulated cell signaling that may predict response to mechanistic target of rapamycin (mTOR) inhibitor therapy such as epidermal growth factor receptor (EGFR) (expression by immunohistochemistry [IHC] and ampl
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]
    Safety will be assessed through summaries of adverse events, changes in selected laboratory test results, changes in vital signs, and TORC1/2 inhibitor MLN0128 and bevacizumab exposure.
  • MTD/RP2D of TORC1/2 inhibitor MLN0128, determined according to incidence of dose-limiting toxicity, as graded using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 28 days ]


Original Primary Outcome:

  • MTD/RP2D of MLN0128, determined according to incidence of dose-limiting toxicity, as graded using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: 28 days ]
  • Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]
    Safety will be assessed through summaries of adverse events, changes in selected laboratory test results, changes in vital signs, and MLN0128 and bevacizumab exposure.


Current Secondary Outcome:

  • Frequency of toxicities leading to missed doses or delays [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Objective RR, defined as a complete or partial response, as determined by investigator assessment using RECIST or RANO [ Time Frame: Up to 1 year ]
  • OS [ Time Frame: Up to 1 year ]
    Listed for all patients by dose level.
  • Percentage of actual planned dosage administration [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Percentage of courses given or not within 7 days of their scheduled times [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Percentage of patients that discontinue study drugs due to treatment related toxicity [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • PFS [ Time Frame: From date of first dose to date of progression or death, assessed at 6 months ]
    Listed for all patients by dose level.


Original Secondary Outcome:

  • PFS [ Time Frame: From date of first dose to date of progression or death, assessed at 6 months ]
    Listed for all patients by dose level.
  • Objective RR, defined as a complete or partial response, as determined by investigator assessment using RECIST or RANO [ Time Frame: Up to 1 year ]
  • OS [ Time Frame: Up to 1 year ]
    Listed for all patients by dose level.
  • Frequency of toxicities leading to missed doses or delays [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Percentage of courses given or not within 7 days of their scheduled times [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Percentage of actual planned dosage administration [ Time Frame: Up to 30 days ]
    Percentage will be summarized.
  • Percentage of patients that discontinue study drugs due to treatment related toxicity [ Time Frame: Up to 30 days ]
    Percentage will be summarized.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 16, 2014
Date Started: May 2014
Date Completion:
Last Updated: May 18, 2017
Last Verified: May 2017