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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01013324
First received: November 10, 2009
Last updated: April 9, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Endometrial Cancer
Endometrial Neoplasms
Drug: XL147 (SAR245408)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of XL147 (SAR245408) in Subjects With Advanced or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Efficacy as defined by overall response rate and progression-free survival (PFS) at 6 months [ Time Frame: every 8-10 weeks ] [ Designated as safety issue: No ]
  • Safety of XL147 in the EC population [ Time Frame: scheduled evaluations every 2-4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of response and PFS [ Time Frame: every 8-10 weeks ] [ Designated as safety issue: No ]
  • Characterize pharmacokinetic and pharmacodynamic profiles of XL147 [ Time Frame: at periodic visits not less than every 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: January 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
All subjects will receive single-agent XL147 dosed daily
Drug: XL147 (SAR245408)
dosed as capsules taken orally daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01013324

Locations
United States, California
Investigational Site Number 1526
Newport Beach, California, United States, 92663
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
Belgium
Investigational Site Number 3212
Kortrijk, Belgium, 8500
Investigational Site Number 3211
Leuven, Belgium, 3000
Investigational Site Number 3218
Wilrijk, Belgium, 2610
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01013324     History of Changes
Other Study ID Numbers: ARD11436, XL147-201
Study First Received: November 10, 2009
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

Additional relevant MeSH terms:
Neoplasms
Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Sarcoma
Neoplasms, Connective and Soft Tissue
Endometrial Stromal Tumors

ClinicalTrials.gov processed this record on July 24, 2014