Clinical Trial: Phase 2 Study of MLN0128, Combination of MLN0128 With MLN1117, Paclitaxel and Combination of MLN0128 With Paclitaxel in Women With Endometrial Cancer

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

Official Title: A Phase 2, Randomized Study of MLN0128 (a Dual TORC1/2 Inhibitor), MLN0128+MLN1117 (a PI3Kα Inhibitor), Weekly Paclitaxel, or the Combination of Weekly Paclitaxel and MLN0128 in Women With Advanc

Brief Summary: The primary purpose of this study is to determine if MLN0128 in combination with weekly paclitaxel improves progression-free survival (PFS) compared to weekly paclitaxel alone.

Detailed Summary:

The drugs being evaluated in this study are MLN0128 and MLN1117. MLN0128 is being evaluated as a single agent and in combination with paclitaxel or MLN1117 to treat women with advanced, recurrent, or persistent endometrial cancer. This study will evaluate the efficacy and safety of each drug or drug combination.

The study will enroll approximately 260 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of 4 treatment groups:

  • Paclitaxel 80 mg/m^2 weekly
  • Paclitaxel 80 mg/m^2 weekly + MLN0128 4 mg 3 consecutive days each week
  • MLN0128 30 mg weekly
  • MLN0128 4 mg + MLN1117 200 mg both given 3 consecutive days each week

Participants will receive either Paclitaxel intravenous (IV) weekly, Paclitaxel IV along with MLN0128 orally, MLN0128 orally, or MLN0128 and MLN1117 orally.

This is a multicenter, multinational trial. Participants will make multiple visits to the clinic, with an end of treatment visit (EOT) which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for PFS and overall survival (OS).


Sponsor: Millennium Pharmaceuticals, Inc.

Current Primary Outcome: Progression Free Survival (PFS) [ Time Frame: Up to 30 months ]

PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease or death due to any cause, whichever occurs first. For a participant who has not progressed and is last known to be alive, PFS will be censored at the last response assessment that is stable disease (SD) or better.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Percentage of Participants who Experience at Least One Treatment-emergent Adverse Event (TEAE) [ Time Frame: From the first dose of study drug through 30 days after the last dose of study drug (Up to 30 Months) ]
  • Overall Survival (OS) [ Time Frame: Up to 30 months ]
    OS is defined as the time from the date of randomization to the date of death. Participants without documentation of death at the time of analysis will be censored at the date last known to be alive.
  • Time to Progression (TTP) [ Time Frame: Up to 30 months ]
    TTP is defined as the time from the date of randomization to the date of first documentation of progression. For a participant who has not progressed, TTP will be censored at the last response assessment that is stable disease (SD) or better.
  • Overall Response Rate (ORR) [ Time Frame: Up to 30 months ]
    ORR is defined as the percentage of participants who achieve a best response of a complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 30 months ]
    CBR is defined as the percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD).
  • Clinical Benefit Rate (CBR) at Week 16 (CBR-16) [ Time Frame: Up to 30 months ]
    CBR-16 is defined as the percentage of participants who achieve CR or PR of any duration or have SD with a duration of at least 16 weeks.


Original Secondary Outcome: Same as current

Information By: Takeda

Dates:
Date Received: March 28, 2016
Date Started: April 1, 2016
Date Completion: August 31, 2018
Last Updated: May 11, 2017
Last Verified: May 2017