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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01013324
Recruitment Status : Completed
First Posted : November 13, 2009
Last Update Posted : June 3, 2016
Information provided by (Responsible Party):

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Endometrial Neoplasms Drug: XL147 (SAR245408) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of XL147 (SAR245408) in Subjects With Advanced or Recurrent Endometrial Carcinoma
Study Start Date : January 2010
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

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

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

Secondary Outcome Measures :
  1. Duration of response and PFS [ Time Frame: every 8-10 weeks ]
  2. Characterize pharmacokinetic and pharmacodynamic profiles of XL147 [ Time Frame: at periodic visits not less than every 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01013324

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

Responsible Party: Sanofi Identifier: NCT01013324     History of Changes
Other Study ID Numbers: ARD11436
XL147-201 ( Other Identifier: (Other study code) )
First Posted: November 13, 2009    Key Record Dates
Last Update Posted: June 3, 2016
Last Verified: May 2016

Keywords provided by Sanofi:
endometrial cancer
endometrial carcinoma
carcinoma of the endometrium
cancer of the endometrium

Additional relevant MeSH terms:
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female