Study of XL147 (SAR245408) in Advanced or Recurrent Endometrial Carcinoma

May 9, 2016 updated by: Sanofi

A Phase 2 Study of XL147 (SAR245408) in Subjects With Advanced or Recurrent Endometrial Carcinoma

There has not been any systemic therapy approved in the United States or in Europe for treating advanced or recurrent endometrial cancer (EC). This study will evaluate the safety and preliminary efficacy of XL147 in advanced or recurrent EC.

Constitutively active phosphatidylinositol-3 kinase (PI3K)/phosphatase and tensin homolog on chromosome 10 (PTEN) pathway signaling is common in EC and involved in the development and/or progression of the disease. PTEN deficiency and/or activating mutations/amplification in the PIK3CA gene that encodes the p110α catalytic subunit of PI3K have been frequently detected in EC patients. XL147 is a potent and highly selective inhibitor of the Class I PI3K family of lipid kinases. In addition, in vivo preclinical data have demonstrated that XL147 targets both proximal and distal signaling in the PI3K/PTEN pathway. Therefore, XL147 may have utility in the treatment of subjects with advanced or recurrent EC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

67

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Kortrijk, Belgium, 8500
        • Investigational Site Number 3212
      • Leuven, Belgium, 3000
        • Investigational Site Number 3211
      • Wilrijk, Belgium, 2610
        • Investigational Site Number 3218
  • United States
    • California
      • Newport Beach, California, United States, 92663
        • Investigational Site Number 1526
    • Florida
      • Orlando, Florida, United States, 32806
        • Investigational Site Number 1532
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Investigational Site Number 1239
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Investigational Site Number 1133
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Investigational Site Number 1325
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73084
        • Investigational Site Number 1434
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Investigational Site Number 1132
      • Philadelphia, Pennsylvania, United States, 19111
        • Investigational Site Number 1134
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Investigational Site Number 1142
    • Texas
      • Dallas, Texas, United States, 75230
        • Investigational Site Number 1527

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • The subject has a histologically confirmed diagnosis of EC (endometrioid, serous, clear cell adenocarcinoma, adenosquamous carcinoma, or mixed histology, any grade) that is advanced (ie, persistent, locally advanced) or recurrent, and is incurable by standard therapies and has received one platinum based chemotherapy regimen for EC.
  • The subject is at least 18 years old.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • The subject has at least one measurable lesion
  • Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
  • The subject has adequate organ and marrow function
  • The subject is capable of understanding the informed consent and complying with the protocol and has signed the informed consent document before any study-specific screening procedures or evaluations are performed.
  • Sexually active subjects of childbearing potential and their partners must agree to use medically accepted methods of contraception during the course of the study and for 3 months after discontinuation of study drug.
  • Subjects of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

  • The subject has previously been treated with a selective PI3K inhibitor, mTOR inhibitor, or AKT inhibitor.
  • The subject has uterine sarcomas (leiomyosarcoma), mixed Mullerian tumors, squamous carcinoma of the uterus, and/or adenosarcomas of the uterus.
  • Certain restrictions on prior treatments apply
  • The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline (excluding alopecia and peripheral neuropathy).
  • The subject has a known primary brain tumor or brain metastasis.
  • The subject has any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix) within 2 years before screening for this study.
  • The subject has a diagnosis of uncontrolled diabetes mellitus or has a fasting plasma glucose > 160 mg/dL.
  • The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤ 1 mg/day is permitted).
  • The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal.
  • The subject has uncontrolled, significant intercurrent illness
  • The subject has a baseline corrected QT interval ≥ 470 ms.
  • The subject is known to be positive for the human immunodeficiency virus (HIV). (Note: Baseline HIV screening is not required.)
  • The subject is pregnant or breastfeeding.
  • The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm
All subjects will receive single-agent XL147 dosed daily
Drug: XL147 (SAR245408)
dosed as capsules taken orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy as defined by overall response rate and progression-free survival (PFS) at 6 months
Time Frame: every 8-10 weeks
every 8-10 weeks
Safety of XL147 in the EC population
Time Frame: scheduled evaluations every 2-4 weeks
scheduled evaluations every 2-4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of response and PFS
Time Frame: every 8-10 weeks
every 8-10 weeks
Characterize pharmacokinetic and pharmacodynamic profiles of XL147
Time Frame: at periodic visits not less than every 4 weeks
at periodic visits not less than every 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

November 10, 2009

First Submitted That Met QC Criteria

November 10, 2009

First Posted (Estimate)

November 13, 2009

Study Record Updates

Last Update Posted (Estimate)

June 3, 2016

Last Update Submitted That Met QC Criteria

May 9, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARD11436
  • XL147-201 (Other Identifier: (Other study code))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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